“Speech and swallowing in MSA and other autonomic disorders”

This article on “Speech and swallowing in MSA and other autonomic disorders” will certainly be of interest to the MSAers but some of the questions/answers will be of interest to everyone (especially #1, #7, #8, #9, #12, and #13). (My dad, with PSP, has many of the problems indicated.)

The Sarah Matheson Trust is a UK charitable organization focused on MSA. The Trust’s newsletter, SMarT News, had an article last year in which “speech and language therapist Tricia Gilpin report(ed) on the presentations of speech and swallowing problems and the therapists role in treating people with MSA.” Here’s a link to the Winter ’05 issue of the newsletter:

Editor’s Note: Link no longer available

There was one surprising sentence in the article: “It is important to realise that exercises will not improve the speech.” I thought that was the whole point of speech therapy. Other than that one quibble, I thought the article was a good introduction to what speech/language pathologists (our term in the US) do and what kinds of speech and swallowing problems there are with these disorders.

A copy of the article follows (note that the numbers in front of the questions were added by me).


Speech and swallowing in MSA and
other autonomic disorders

by Tricia Gilpin
Senior Speech and Language Therapist
SMarT News, Winter ’05 Issue, November 2005
Sarah Matheson Trust newsletter

#1 What does a Speech & Language
Therapist do?

Speech and Language Therapists are
involved with both children and adults
with many different types of disorders.
These include developmental difficulties,
stroke, head injury, brain
tumours and many different degenerative
neurological diseases.

The SLT will see patients with any
of the following problems:

* Dysarthria: a motor speech
disorder, where there is loss of
function or co-ordination in the
breathing mechanism, or in the lips,
tongue or soft palate

* Dysphasia: a disruption to the
language centre in the brain which
may affect understanding of the
spoken word, spoken output,
reading & writing

* Dysphonia: the loss of the voice
due to physical or psychological
difficulties. This must always be
checked by an Ear, Nose and Throat
specialist to eliminate the possibility
of structural damage to the larynx

* Dyspraxia: a motor speech
programming disorder. There is no
loss of movement in the lips,
tongue or soft palate, but the
messages from the brain to them
becomes disrupted

* Dysphagia: this is a disturbance in
the process of swallowing. A person
with dysphagia may report any of
the following signs:
– difficulty with hard, dry foods or
mixed consistencies
– problems with thin liquids
– coughing and choking when
eating and drinking
– food becoming stuck in the mouth
or falling out of the mouth
– extended meal times
– excessive saliva and/or dribbling
– having a ‘gurgly’ voice after
mealtimes or drinks
– difficulty opening the mouth
– weak cough
– weight loss
– chest infection

* Tracheostomy: SLTs also work
with patients who have a

#2 Classification of Multiple
System Atrophy

There are three different aspects to

* Parkinsonian or Extrapyramidal signs
* Cerebellar signs
* Autonomic Impairment

The disease can present in any of
these three ways, or often as a
combination of two or three of them.
The speech and swallowing
characteristics of the patient will vary
according to the clinical picture, and
may change over time.

#3 What speech characteristics
should I expect if the presentation
is mainly Parkinsonian?

This type of MSA is now called MSA-P.
The type of dysarthria seen in
Parkinson’s Disease, and in MSA-P is
called hypokinetic dysarthria. This is
characterised by:

* festination of speech — that is
difficulty getting started and then
speech coming out in a rush

* quiet speech

* slow and hesitant speech

* speaking in a monotone and at the
same pitch

#4 What should I expect if the
presentation is mainly

This used to be called Olivopontocerebellar
Atrophy but is now
called MSA-C.

This type of MSA involves the
cerebellum and brain stem and the type
of dysarthria seen is called ataxic or
cerebellar dysarthria. This is
characterised by:
* staccato (or chopped up) speech
* imprecise consonants
* slow and slurred speech

Unfortunately, this type of dysarthria
can make you sound as if you have been
drinking too much alcohol.

#5 What if it is the Autonomic

The third type of MSA is the
predominantly Autonomic presentation
where the patient often has postural
hypo-tension. This may lead to general
feelings of dizziness and exhaustion
and you may not feel very much like
talking at all.

A drop in the blood pressure can
result in a decrease in the volume of
the speech.

#6 Spastic Dysarthria

In addition some patients present with a
spastic dysarthria where the speech is
characterised by:
* imprecise consonants
* strained or strangled voice
* quiet voice

It is important to remember that speech
characteristics in MSA can be mixed
between the different types of
presentation and therefore the different
types of dysarthria.

A research study by Kluin et al in
1996 looked at 46 patients with MSA
and looked at the speech characteristics
and concluded that:

* Hypokinetic components
predominated in 48%
* Ataxic components predominated in
* Spastic components predominated
in 11%
* the remaining 6% were mixed

#7 What can the SLT do to assess
my speech and communication?

The SLT may decide to do a formal
dysarthria assessment. This consists of
looking at the different aspects of the
speech process:
* respiration (breathing for speech)
* phonation (production of sound)
* movements of the facial musculature
* prosody (intonation patterns — the
ability to change pitch in speech)
* articulation (ability to produce clear
* intelligibility

Alternatively, the SLT may assess you
in a more informal way by talking to
you and to your family.

#8 What can the SLT do to help me
with my speech and

Unfortunately, there is no cure for
the speech difficulties experienced in
MSA but the SLT can help by giving
information to the patient and to
the family.

Many people with MSA experience
other difficulties with their
communication in addition to the

* many people experience a lack of
facial expression

* others find making and maintaining
eye contact difficult

* some may have a forward head tilt
which hampers communication,
feeding and vision

* others will have displays of
inappropriate laughter or crying

* some people have difficulty
switching attention from one topic
to another

* some people will experience a
low mood

Often it is helpful just to be able to
discuss these matters and try to find a
way, with the therapist, to manage these
difficulties. It can be helpful to discuss
ways to avoid very noisy situations, or
to cut down on background noise when
trying to communicate (even turning off
the TV can be helpful).

For the family and friends of the
person with MSA it is important to try
to make time to communicate, even
though the process may be slower
than previously. It is often helpful to
be able to watch the face of the
person to help with understanding and
to ask for repetition in a different
way if something cannot be understood.
It is important not to pretend to
understand if you have not, and to ask
for clarification.

#9 Will the SLT give me exercises to
do to improve my speech?

It is important to realise that exercises
will not improve the speech. However,
sometimes the therapist will decide to
focus on a particular aspect of the
speech mechanism to try to maintain
and preserve speech for as long as
possible. It may be helpful to work on:

* exercises to improve facial

* breathing exercises to maintain an
adequate respiratory drive for speech

* relaxation exercises to reduce
tension in the muscles used for

* voice exercises to maximise volume

* speech exercises to improve overall
intelligibility and fluency

#10 Are there any Communication
Aids for people with MSA?

* some people find that a small speech
amplifier can be helpful

* there are other communication aids
such as Lightwriters which allow the
patient to type out their message and
the machine talks for them

* some people prefer to use a pen and
paper if they are finding speech

#11 I have heard that sometimes
people with MSA need to have a
tracheostomy. Is this true?

Unfortunately, some patients with MSA
may experience difficulty opening the
vocal cords in the larynx sufficiently to
allow the normal amount of airflow.

This may be due to vocal cord palsy and
can result in:
* excessive snoring
* inspirational stridor — a sound like
snoring but on the ‘in’ breath
* sleep difficulties and vivid dreams
* breathing problems, particularly at
* sleep apnoea, where the person stops
breathing for a short time during

In extreme cases the ENT surgeon may
recommend a tracheostomy. This is a
small tube which is fitted into the
neck below the level of the vocal cords,
allowing the patient to breathe

The Speech and Language Therapist
can assist in advising whether or not a
speaking valve is appropriate.

#12 What happens to the normal
swallow in people who have

The normal swallow is made up of 3
* the oral stage
* the pharyngeal stage
* the oesophageal stage

All three stages of the swallow may be
disrupted in MSA. A research study by
Smith & Bryan in 1992 looked at ten
patients with MSA and found the

Oral stage:
* 90% had decreased control of what
was in their mouth
* 40% had poor tongue movements

Pharyngeal stage:
* 80% had a delayed swallow
* 100% reported the feeling of
‘something stuck in the throat’
* 30% experienced ‘silent’ aspiration —
where food or drink goes ‘down the
wrong way’ and enters the lungs, but
the patient does not cough

Oesophageal stage:
* some patients with MSA or other
types of autonomic dysfunction
experience dysmotility of the gut
* this can result in constipation but
also in dysmotility of the
oesophagus with patients reporting a
feeling of ‘something stuck’ in the
centre of their chest

#13 How will the Speech and
Language Therapist assess my

The SLT will start by taking a full
history of the disease process and also
of the eating and swallowing problems
>from both the patient, and if possible,
>from the carers.

The SLT will then probably
complete the following assessments:

* a ‘bedside’ assessment of the
swallow including:
– assessing the cranial nerves of the
patient, looking at the functioning
of the face, tongue, lips, soft
palate etc.
– trial the patient on various foods
and drinks, observing their ability
to cope with different

* possibly perform a videofluoroscopy
(this is a moving x-ray of the
swallow which is filmed onto
video). This shows the safety and
assist the therapist in making
recommendations regarding:
– appropriate consistencies of food
– positioning
– possible modifications to the diet

It may be that the SLT, in consultation
with other members of the multidisciplinary
team, may suggest a PEG.
This is a Percutaneous Enderscopic
Gastrostomy which is a small tube
which is passed directly into the
stomach to allow the patient to be fed
with liquid feed, should this become

A PEG is often used in conjunction
with continuing to eat and drink. It may
be that the patient is finding eating and
drinking very time consuming, slow and
difficult and may find it much more
pleasurable to get all the necessary
hydration and nutrition through the PEG
leaving the opportunity to eat and/or
drink small amounts for pleasure.

#14 The Multi-Disciplinary Team and
the Speech and Language

The SLT may discuss a number of
complex issues with you regarding
your speech and swallowing and
also have discussions with you
regarding the placing of a PEG tube or
a tracheostomy.

It is important to remember that any
complex decision that has to be made
will always be after joint discussion
between members of the MDT, the
patient and his/her family. The MDT
may include the Neurologist, the GP, the
clinical nurse specialist for MSA, other
nurses, the dietician, the physiotherapist,
the occupational therapist and the speech
and language therapist.

In the discussions regarding the
placement of a PEG or a tracheostomy
it is vital to allow time for discussion
with the patient and his family and to
take into account the individuals right to
make decisions about his or her quality
of life.

New Zealand Pamphlet on MSA

On the Shy-Drager online support group today, Vera posted a link to a pamphlet done by the Parkinsonism Society of New Zealand on multiple system atrophy (MSA).  The link is:


Editor’s Note: Link is no longer active

This short pamphlet would be something you could send to family members to provide a general introduction to MSA.  Or it could be given to new caregivers.

Copied below is most of the inside page of the 2-page New Zealand pamphlet that gives details on MSA.



What is MSA?
Multiple system atrophy (MSA) is a rare
progressive neurological disorder presenting
with similar symptoms to Parkinson’s disease.
The condition is marked by a combination of
symptoms affecting movement, blood
pressure, and other body functions; hence the
label multiple system atrophy.

Various forms of MSA
Symptoms of MSA vary from person to
person. Because of this, three different
diseases were initially described to encompass
this range of symptoms: Shy-Drager
syndrome, striatonigral degeneration, and
olivopontocerebellar atrophy.

What causes MSA?
The cause of MSA is unknown.

Symptoms of MSA?
MSA can cause a wide range of symptoms,
.. orthostatic hypotension, or a significant fall
in blood pressure when standing, causing
dizziness, lightheadedness, fainting, or
blurred vision
.. male impotence
.. loss of control of bowel or bladder
.. stiffness or rigidity
.. freezing or slowed movements
.. postural instability; loss of balance; lack of
.. speech and swallowing difficulties blurred
.. changes in facial expression.

Who gets MSA?
MSA usually starts between the ages of 50-60
years, although it can affect people younger and
older than this. Around 4 in 100,000 people
are affected by MSA in New Zealand. MSA
does not appear to be hereditary and is not
infectious or contagious. It is a sporadic
disorder that occurs at random.

How is MSA diagnosed?
Often symptoms are vague and diagnosis is
difficult. MSA is often mistaken for Parkinson’s,
especially in the early stages of the condition.
Diagnosis should be made by a specialist,
usually a neurologist.

What is the treatment?
Currently there is no specific treatment for
MSA. A variety of medications, including some
drugs used for Parkinson’s, and other forms of
therapy can help control the symptoms.
Treatment may focus on alleviating the
symptoms, so people with MSA could benefit
>from working with physiotherapists, speech
therapists, dieticians, continence nurses, and
occupational therapists.

What is the prognosis?
MSA is a progressive disorder, the rate of
progression differs in every person.

To the person with MSA and their
The diagnosis of MSA has significant impact
on those close to the patient. As the
condition progresses so does the need for
care. Carers/families may feel isolated,
frustrated and chronically tired. Infinite
patience is needed. Carers/families will
need support and should utilise support
services. Support services can be contacted
directly or referral can be made through
your doctor or health professional.

April 2005 FDA Warning on Antipsychotics w/Dementia

This FDA black box warning from April 2005 applies to everyone with

It addresses these medications: olanzapine (Zyprexa), aripiprazole
(Abilify), risperidone (Risperdal), quetiapine (Seroquel), clozapine
(Clozaril), ziprasidone (Geodon), and Symbyax.

Here’s the FDA warning from last year:
FDA Public Health Advisory
Date created: 4/11/05
Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances

The Food and Drug Administration has determined that the treatment of
behavioral disorders in elderly patients with dementia with atypical
(second generation) antipsychotic medications is associated with
increased mortality. Of a total of seventeen placebo controlled trials
performed with olanzapine (Zyprexa), aripiprazole (Abilify), risperidone
(Risperdal), or quetiapine (Seroquel) in elderly demented patients with
behavioral disorders, fifteen showed numerical increases in mortality in
the drug-treated group compared to the placebo-treated patients. These
studies enrolled a total of 5106 patients, and several analyses have
demonstrated an approximately 1.6-1.7 fold increase in mortality in
these studies. Examination of the specific causes of these deaths
revealed that most were either due to heart related events (e.g., heart
failure, sudden death) or infections (mostly pneumonia).

The atypical antipsychotics fall into three drug classes based on their
chemical structure. Because the increase in mortality was seen with
atypical antipsychotic medications in all three chemical classes, the
Agency has concluded that the effect is probably related to the common
pharmacologic effects of all atypical antipsychotic medications,
including those that have not been systematically studied in the
dementia population. In addition to the drugs that were studied, the
atypical antipsychotic medications include clozapine (Clozaril) and
ziprasidone (Geodon). All of the atypical antipsychotics are approved
for the treatment of schizophrenia. None, however, is approved for the
treatment of behavioral disorders in patients with dementia. Because of
these findings, the Agency will ask the manufacturers of these drugs to
include a Boxed Warning in their labeling describing this risk and
noting that these drugs are not approved for this indication. Symbyax, a
combination product containing olanzapine and fluoxetine, approved for
the treatment of depressive episodes associated with bipolar disorder,
will also be included in the request.

The Agency is also considering adding a similar warning to the labeling
for older antipsychotic medications because the limited data available
suggest a similar increase in mortality for these drugs.


Here’s an article written on the FDA warning in the “Senior Journal”:

FDA Warns Antipsychotic Drugs Dangerous to Elderly With Dementia

April 14, 2005 – The Food and Drug Administration (FDA) this week issued
a public health advisory to alert health care providers, patients, and
patient caregivers to new safety information concerning an unapproved
(i.e., “off-label”) use of certain drugs called “atypical antipsychotic
drugs.” These drugs are approved for the treatment of schizophrenia and
mania, but clinical studies of these drugs to treat behavioral disorders
in elderly patients with dementia have shown a higher death rate
associated with their use compared to patients receiving a placebo
(sugar pill).

The advisory applies to such antipsychotic drugs as Abilify
(aripiprazole), Zyprexa (olanzapine), Seroquel (quetiapine), Risperdal
(risperidone), Clozaril (clozapine) and Geodon (ziprasidone). Symbyax,
which is approved for treatment of depressive episodes associated with
bipolar disorder is also included in the agency’s advisory.

FDA is requesting that the manufacturers of all of these kinds of drugs
add a boxed warning to their drug labeling describing this risk and
noting that these drugs are not approved for the treatment of behavioral
symptoms in elderly patients with dementia. Patients receiving these
drugs for treatment of behavioral disorders associated with dementia
should have their treatment reviewed by their health care providers.

In analyses of seventeen placebo-controlled studies of four drugs in
this class, the rate of death for those elderly patients with dementia
was about 1.6 to 1.7 times that of placebo. Although the causes of death
were varied, most seemed to be either heart-related (such as heart
failure or sudden death) or from infections (pneumonia).

The atypical antipsychotics fall into three drug classes based on their
chemical structure. Because the increase in mortality was seen with
atypical antipsychotic medications in all three chemical classes, the
agency has concluded that the effect is probably related to the common
pharmacologic effects of all atypical antipsychotic medications,
including those that have not been studied in the dementia population.

The agency is considering adding a warning to the labeling of older
antipsychotic medications because limited data also suggest a similar
increase in mortality for these drugs. The review of the data on these
older drugs, however, is still on-going.

You can find patient information sheets and healthcare provider sheets
on all of the drugs mentioned at this FDA web page:


Consumers can call: 888-INFO-FDA.


Treating incontinence by injecting muscle stem cells

This not-yet-available in the US treatment for urinary incontinence may be of interest to many in the group…

Beth (with multiple system atrophy)) had another interesting post recently on an MSA-related list. I’ve gotten her permission again to copy it below.

She includes an abstract from a 5/21/06 American Urological Association meeting. The abstract summarizes two clinical studies done in Austria and Canada on injecting muscle stem cells to treat urinary incontinence. Roger Dmochowski, MD, a professor with the Dept of Urology at Vanderbilt University in Nashville, moderated a press conference on urinary incontinence at the meeting. He said two interesting things:

* “The technique is minimally invasive compared to surgical treatments for urinary incontinence. Once it gets traction, it could go rapidly into the practice arena.”

* Some larger studies will be beginning very soon in the United States.

If you want to keep an eye out for possible trials in the US, you can: 1) watch and search on clinicaltrials.org, using “urinary incontinence” as the search term, 2) watch Medscape’s weekly newsletters, and 3) go to a medical library or go online to review announcements put out by major urology journals.


From: Beth Klitch
Date: Tue May 30, 2006 6:01pm(PDT)
Subject: Exciting new treatment for urinary incontinence – Injection of muscle stem cells

Urinary incontinence is another common condition that we MSA patients experience. Some of us respond to medications such as Flomax that reduce the bladder spasms that can cause urge incontinence. Some of us may undergo surgery to have devices such as Medtronic’s InterStim device implanted to send electrical signals to the sacral nerves that help stimulate the bladder to contract. Many more of us find ourselves isolated or fearful of incontinence accidents and thus we pass up opportunities to travel outside our homes or to visit friends.

Earlier this month, the American Urological Association met and heard reports about a wide range of topics that affect the urinary tract. I have included an extended summary of some exciting research that is underway to treat and actually cure urinary incontinence. Note that the first two clinical studies were performed in Austria and Canada and that larger trials are planned for the United States in upcoming months. This may be an opportunity to volunteer to take part in a clinical trial that has high potential to improve the quality of our lives. Also note that the results were significantly better for women than men and that there are some risks to any surgical procedures, even ones that are minimally invasive.


May 22, 2006 (Atlanta) ­ Injection of muscle stem cells into the suburethral mucosa may be effective for the treatment of urinary incontinence, according to findings from 2 clinical studies. Hannes Strasser, MD, from the Universitatsklinik fur Urologie, Medizinische Universitat Innsbruck, Austria, and colleagues reported their findings here at the American Urological Association 2006 Annual Meeting.

Injecting stem cells into the urethral submucosa is expected to alleviate atrophy of the submucosa by potentially boosting the contractility of the muscle tissue and improving urethral function. In the study, a total of 130 patients (45 men and 85 women) with stress or mixed urinary incontinence were treated with transurethral ultrasound­guided injections. Patients were aged 36 to 85 years. Changes in morphology and function of the urethra and rhabdosphincter and quality of life were evaluated.

While under local anesthesia, patients had small skeletal muscle biopsies taken from their upper arm. Cells from the sample were cultured, and fibroblasts were eventually mixed with about 2.5 mL of collagen, which served as carrier material. With the aid of a transurethral ultrasound probe and injection device, the fibroblasts were introduced into the urethral submucosa. The myoblasts were directly injected into the rhabdosphincter to reconstruct the muscle.

Urinary incontinence was cured after injection of stem cells in 111 (79 women, 32 men) of the 130 patients. Therapy was able to increase the thickness of the urethra and the rhabdosphincter as well as increase the activity and contractility of the rhabdosphincter. An additional 17 patients experienced an improvement but not complete relief of incontinence.

Significant improvements in quality of life were also observed after treatment, and the therapy appeared to be well tolerated. No adverse effects or complications were observed. Dr. Strasser noted that further follow-up indicated that 1 patient had a major complication ­ a perforation in a male patient who had undergone several surgeries and radiation therapy.

According to Dr. Strasser, the efficacy of this technique is better in women than men, possibly for 2 reasons: the injection is easier in women due to the shorter length of the urethra. The second is that after radical prostatectomy in men, changes such as scarring can take place in the urethra. “In females the efficacy rate is more than 90%, whereas in males the efficacy rate is about 72% to 73%,” he told Medscape.

The therapeutic effect appeared to be long-lasting. “The full effect of the therapy takes about 3 to 4 weeks to achieve, whereas other injectable therapies can take effect immediately,” he said. “However, the vast majority of patients who do well 3 months after therapy remain stable. These patients are still continent, meaning they don’t need pads.”

A smaller, North American study evaluating a similar procedure was reported by Lesley K. Carr, MD, from the University of Toronto, Ontario, Canada, and colleagues. Six women, aged 41 to 66 years, with stress urinary incontinence, were treated with either a trans- or periurethral injection technique; one of the patients was reinjected after 6 months.

Skeletal muscle tissue was taken from each patient with a needle biopsy technique. Muscle-derived cells were then isolated and expanded in culture. After at least 1 month of follow-up, no improvement was observed in patients treated with a smaller (8 mm) cystoscopic injection needle. However, 2 subsequent transurethral injections using a longer needle (10 mm) and the 2 periurethral injections did result in improvement in 4 patients, who all reported an improvement in quality of life.

“We hypothesize that the injected muscle-derived cells differentiated into new muscle fibers and improved muscle function, but the exact mechanisms of these actions are still being investigated,” note Dr. Carr and colleagues in their abstract. “Improvements to the delivery technique may have contributed to a greater success rate in the most recently injected patients.” Again, no adverse effects were noted.

Roger Dmochowski, MD, a professor with the Department of Urology at Vanderbilt University in Nashville, Tennessee, noted that the results seen with this technique are “very encouraging,” although he pointed out that various injection techniques and different types of cells are being studied, “making it difficult to compare results.”

Several centers in Europe are experimenting with autologous muscle stem cell injection, and some larger studies will be beginning very soon in the United States, noted Dr. Dmochowski, who moderated a press conference on urinary incontinence at the meeting. “The technique is minimally invasive compared to surgical treatments for urinary incontinence,” Dr. Dmochowski added. “Once it gets traction, it could go rapidly into the practice arena.”

AUA 2006 Annual Meeting: Abstracts 328 and 1284. Presented May 21, 2006.

Drug treatment for orthostatic hypotension

This will likely be of interest to the MSA folks or those with orthostatic hypotension as a symptom….

Beth Klitch has MSA. She lives in the Midwest. She posted this recently on an MSA digest; it’s about the success seen by Japanese researchers using an FDA-approved diabetes drug to treat post-prandial hypotension. I asked her permission to copy the post here because I think it may be useful to some of our group members.

To find the three-sentence Neurology journal article abstract the post below refers to, go to www.neurology.org and search for “voglibose.”


From: Beth Klitch
Date: Tue May 30, 2006 5:44pm(PDT)
Subject: Exciting new use of an existing drug to treat hypotension after meal

Since many of us with MSA suffer from severe orthostatic hypotension, me included, I keep a close eye on research reports about medications and other treatments that may be available to help us treat this condition. Just a few days ago, an interesting report surfaced in Neurology 2006;66:1432-1434 about a drug primarily used to treat diabetes, but which has profound implications to help treat the hypotension that occurs right after eating a meal, also called post-prandial hypotension. Note that MSA patients were included in this research along with Parkinson’s patients and patients with diabetes.

I have shared the article summary below for those who are interested. I think this is potentially great news for us because it is another example of an existing drug that can be extended to treat an additional condition and has already met the FDA’s safety and efficacy standards. The drug is called Voglibose, is marketed as Volix, and is considered one of the most important alpha-glucosidase inhibitors. It works in treating diabetes by delaying the digestion and absorption of carbohydrates, thereby decreasing the rise in glucose levels and insulin levels that typically occur after eating a meal.


NEW YORK (Reuters Health) May 24 – The alpha-glucosidase inhibitor voglibose can help reduce postprandial hypotension, Japanese researchers report in the May 9th issue of Neurology. Lead investigator Dr. Takahiro Maruta of Kanazawa University and colleagues note that reduced blood pressure after a meal is common in the elderly and in those with conditions such as Parkinson’s disease and diabetes mellitus. It can increase the risk of falls and coronary events.

To examine the effect of voglibose on postprandial hypotension, the researchers studied 48 elderly subjects including those with Parkinson’s disease, multiple system atrophy and diabetes as well as elderly and younger controls with no autonomic disorder. Within 2 hours of 75-g glucose loading, blood pressure fell by more than 20 mm Hg in 72.7% of the Parkinson’s patients, all of those with multiple system atrophy, 27.3% of the patients with diabetes, 23% of the elderly controls and none of the younger controls.

Following voglibose administration, there was a significant reduction in this drop in blood pressure. Without voglibose the mean drop was 41.5 mm Hg; with voglibose, it was 21.0 mm Hg. There was also a reduction in the duration of postprandial hypotension under the two conditions (52.3 minutes versus 17.3 minutes).

Summing up Dr. Maruta told Reuters Health, “Many people suffer from symptoms due to hypotension. Our research should cast some light on ways to help them.”

Journal article on MRIs to distinguish PSP, MSA, and PD

This article in the Movement Disorder Society magazine (of the UK) is on using MRIs to distinguish between Progressive supranuclear palsy (PSP), Multiple system atrophy (MSA), and Parkinson’s disease (PD). Apparently the technique is most (only?) effective in later stages. This was published online on 4/6/06. The abstract is below.



Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico-radiological correlations
Dominic C. Paviour, MRCP, Shona L. Price, BSc, Marjan Jahanshahi, PhD , Andrew J. Lees, MD, FRCP , Nick C. Fox, MD, FRCP

Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders, each with a prevalence of around 5 per 100,000. Regional brain atrophy patterns differ in the two disorders, however, and magnetic resonance imaging is sometimes helpful in distinguishing them in the later stages. We measured whole brain and regional volumes, including cerebellum, pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as well as frontal and posterior-inferior cerebral regions in 18 subjects with PSP, 9 with MSA-P (parkinsonian phenotype), 9 with Parkinson’s disease (PD), and 18 healthy controls. Associations between these volumes, cognitive profiles, and clinical measures of disease severity and motor disability were assessed. Mean midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15% smaller than in MSA-P (P = 0.009). The mean SCP volume in PSP was 30% smaller than in MSA-P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA-P were 20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean pontine volume in MSA-P was 30% smaller than in PD or controls (P < 0.001) and 25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated with midbrain volume, and more severe executive dysfunction was associated with reduced frontal volume. These distinct patterns of cortical and subcortical atrophy, when considered together rather than independently, better differentiate PSP and MSA-P from each other and also from healthy controls. © 2006 Movement Disorder Society

Points from an expert physical therapist – on PD and parkinsonism

I attended Marilyn Basham’s presentation this afternoon on “Caregiving Made Easy for Parkinson’s Individuals.”  She’s the physical therapist (PT) at The Parkinson’s Institute (TPI).  I picked up a few tidbits at the presentation that I thought I’d pass along.  As the presentation was focused on Parkinson’s Disease (PD), not everything applied to the situations we are dealing with but there were still many interesting points that apply.

Here are the points I found interesting….  (with some of my comments in parantheses)

People with PD and Parkinsonism MUST use a walker or wheelchair to make them as safe as possible.  It’s very important to have mobility and postural strategies worked out with a physical therapist and/or neurologist.

PD is evident when 60-80% of the cells in the basal ganglia have died.

The “automatic motor programs” we have are stored in the basal ganglia.  One of these “programs” is what tells us that to stand up from a low chair, we need to scoot to the edge, put our feet underneath us, lean forward, and push up.  PD folks must either receive cues as to the steps of these programs, or they must practice it so many times that doing it becomes somewhat automatic again.

To overcome freezing (called “gait initiation failure”), you can put masking tape on the floor to provide a visual cue.  Put the tape at thresholds or where ever the person often has the freezing problem.  (Of course this won’t work for those with PSP who have downward gaze palsy.)

A suggested verbal cue to give someone who wants to speak is:  “Swallow.”  (pause to let the person swallow)  “Take a deep breath in and then, at the top of your breath tell me what you want.”  (pause to let this happen)  Swallowing is important because fluid accumulates in the back of the throat and those with PD are not aware of it.  You can give them gum to initiate a swallow response.

Before someone with MSA (or PD with blood pressure fluctuations) stands up, give them a glass of water with salt in it or Gatoraid.  This will increase the blood pressure.  Obviously the person’s diet and blood pressure medication needs to be taken into account before following this suggestion.

We must give time for those with these diseases to process information!  Be patient!  Give long pauses.  Don’t overload them.  Don’t give them more than one complex task at a time.  Walking is a complex task.

(Some of you know that my father and I communicate by our holding up fingers to designate an answer.  Example, “do you want 1 for coffee, 2 for tea, or 3 for nothing,” and I hold up 1, 2, and 3 fingers.  He answers by holding up fingers.  Long after the fingers come up, he may try to verbalize the answer.)  I asked Marilyn why my father could hold up fingers faster than he could verbalize a response.  Marilyn said she didn’t know why but pointed out that parents of small children teach their children sign language long before the children can verbalize.

Dementia is rare in PD.  (It’s definitely common in the Atypical Parkinsonism diseases.)  PD folks may lose their keys but they still remember what keys are and how to use them.  (I thought that was a good story for remembering what dementia is.  My dad, for example, cannot remember how to use an ATM card.  I see the dementia very clearly.)

A patch for Sinemet is in the works.  (Some of your loved ones take Sinemet.)

The head of TPI thinks that PD is the most curable of all the neurodegenerative diseases.  (Let’s hope he’s right because hopefully those diseases related to PD can be cured quickly too.)


Theoretical benefit of DBS with PSP and MSA

For those with not enough reading materials(!), neurologyreviews.com is an interesting website.  In the January 2006 News Roundup section of the website, there’s an article about how deep brain stimulation in specific areas could help those with multiple system atrophy or progressive supranuclear palsy.

A short blurb is copied below.




Two studies in the November 28, 2005, NeuroReport demonstrated that the pedunculopontine nucleus can be targeted safely and effectively with deep brain stimulation without major surgical risks in patients with Parkinson’s disease. Low frequency (20 to 25 Hz) stimulation of the pedunculopontine nucleus improves postural stability and gait disturbance, including “on-medication” freezing. Furthermore, combined stimulation of the subthalamic nucleus and the pedunculopontine nucleus appears to be more valuable than stimulation of the pedunculopontine nucleus alone. “In theory, even patients with multiple system atrophy or progressive supranuclear palsy could benefit [from this treatment]­in fact, any patient with intractable locomotive and postural akinesia [could benefit],” reported the investigators.

PSP and MSA can occasionally co-exist

An article was published earlier this week in a medical journal for neuropathologists.  Here’s the key point of this abstract:

“Based upon the findings in this case, the neuropathologic changes of PSP and MSA are distinct and independent processes, but they can occasionally coexist.”

Obviously these things can ONLY be known through brain donation.  I hope everyone in our group will consider that.

I’ve copied the full abstract below.


Acta Neuropathologica (Berlin).  2006 Feb 3; 1-7.

Coexistence of PSP and MSA: a case report and review of the literature.

Uchikado H, Delledonne A, Uitti R, Dickson DW

Department of Neuroscience, Neuropathology Laboratory, Mayo Clinic, 4500 San
Pablo Road, Jacksonville, FL, 32224, USA,  [email protected]

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy characterized by Parkinsonism, vertical gaze palsy,  and early falls. The neuropathology is characterized by neurofibrillary tangles, tufted astrocytes, and
coiled bodies, but some brains show other pathologic processes. To investigate the frequency of alpha-synuclein pathology in PSP with immunohistochemistry and to report the clinical and pathological features of a case of PSP with
concomitant Multiple system atrophy (MSA) (PSP/MSA), 290 cases of PSP were screened for alpha-synuclein pathology withi mmunohistochemistry.  Double-labeling
immunohistochemistry was performed on a case of PSP/MSA. Among the PSP cases screened for alpha-synuclein pathology, a single case of PSP/MSA  was detected. The patient was an 86-year-old woman with clinical features consistent with PSP. She had no documented dysautonomia or cerebellar signs, and imaging studies were not diagnostic of MSA. Pathological examination showed tau-immunoreactive neuronal and glial lesions consistent with PSP as well as alpha-synuclein immunoreactive glial cytoplasmic inclusions diagnostic of MSA. Double-immunolabeling studies showed no co-localization of alpha-synuclein and tau in
most neuronal and glial lesions. Based upon the findings in this case, the neuropathologic changes of PSP and MSA are distinct and independent processes, but they can occasionally coexist.


Two distinct types of PSP – RS and PSP-parkinsonism

Here’s the citation to a very important paper published recently on progressive supranuclear palsy (PSP):

Brain. 2005 Jun;128(Pt 6):1247-58. Epub 2005 Mar 23. 
Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism.
Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC, Kilford L, Holton JL, Revesz T, Lees AJ.
The Queen Square Brain Bank for Neurological Disorders, University College London, UK.

Dr. David Williams and others from The Queen Square Brain Bank in London examined the brains and clinical records of 103 people with autopsy-confirmed PSP.  They discovered two key clinical types of PSP:  Richardson’s Syndrome and PSP-parkinsonism.

The authors described Richardson’s Syndrome (RS) as follows:

“The core clinical features of PSP appears to be bradykinesia, rigidity and postural instability, and are almost always present later in the disease.  Together with the supranuclear vertical ophthalmoplegia, dementia, dysarthria and pseudobulbar palsy, they form the classic features of PSP.  When these features appear in the first 2 years, a diagnosis of RS is most likely.”

The authors described the PSP-parkinsonism type as follows:

“The features which most clearly differentiate this syndrome from RS appear to be an asymmetric onset, extra-axial dystonia, tremor and benefit from levodopa.  Early bradykinesia appears to be essential for the diagnosis, but does not adequately differentiate it from RS, especially later in the disease course.  Disease duration in PSP-P is significantly longer than in RS, and to our knowledge exceeds median survival in all clinicopathological PSP case series.”

Here’s the abstract to this important paper:  (broken into paragraphs)

“The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification of characteristic signs and symptoms. A proportion of pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life and are considered as atypical PSP. The aim of this study was to examine the apparent clinical dichotomy between typical and atypical PSP, and to compare the biochemical and genetic characteristics of these groups.

In 103 consecutive cases of pathologically confirmed PSP, we have identified two clinical phenotypes by factor analysis which we have named Richardson’s syndrome (RS) and PSP-parkinsonism (PSP-P). Cases of RS syndrome made up 54% of all cases, and were characterized by the early onset of postural instability and falls, supranuclear vertical gaze palsy and cognitive dysfunction. A second group of 33 (32%) were characterized by asymmetric onset, tremor, a moderate initial therapeutic response to levodopa and were frequently confused with Parkinson’s disease (PSP-P). Fourteen cases (14%) could not be separated according to these criteria. In RS, two-thirds of cases were men, whereas the sex distribution in PSP-P was even. Disease duration in RS was significantly shorter (5.9 versus 9.1 years, P < 0.001) and age at death earlier (72.1 versus 75.5 years, P = 0.01) than in PSP-P.

The isoform composition of insoluble tangle-tau isolated from the basal pons also differed significantly. In RS, the mean four-repeat:three-repeat tau ratio was 2.84 and in PSP-P it was 1.63 (P < 0.003). The effect of the H1,H1 PSP susceptibility genotype appeared stronger in RS than in PSP-P (odds ratio 13.2 versus 4.5). The difference in genotype frequencies between the clinical subgroups was not significant. There were no differences in apolipoprotein E genotypes.

The classic clinical description of PSP, which includes supranuclear gaze palsy, early falls and dementia, does not adequately describe one-third of cases in this series of pathologically confirmed cases. We propose that PSP-P represents a second discrete clinical phenotype that needs to be clinically distinguished from classical PSP (RS). The different tau isoform deposition in the basal pons suggests that this may ultimately prove to be a discrete nosological entity.”

From my reading, the PSP-parkinsonism type of PSP looks like Parkinson’s Disease and may look like MSA, specifically the parkinsonism type (MSA-P).

According to the full article, some people with PSP actually had a response to levodopa therapy!  Do the diagnostic criteria need to be changed to accommodate this finding?


Update from 2007:

This important paper is now available online at no cost.

Here’s the direct link to the Brain ’05 article:


And I think the commentary is worth reading too: