Category Archives: CBD

‘Bicycle Sign’ May Distinguish PD From Atypical Parkinsonism

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This is a news article based upon some new research published in the latest issue of The Lancet. “New research suggests the preserved ability to ride a bicycle after onset of symptoms may accurately differentiate between Parkinson’s disease (PD) and atypical parkinsonism,” such as PSP, CBD, MSA, LBD, and vascular parkinsonism.

“Making the differential diagnosis … is important clinically for counseling patients and accurate inclusion of suitable patients into trials but remains challenging,” the researchers note. “Here, we suggest that the answer to 1 simple question — ‘Can you still ride a bicycle?” — offers good diagnostic value for separating Parkinson’s disease from atypical parkinsonism.”

Could it be this easy?

The short, two-page article in The Lancet is available at present at no charge online. See:
http://www.thelancet.com/journals/lance … 40-6736(11)60018-4/fulltext

The table is worth a quick look.

Here’s a link to the news article in Medscape and the full text.

Robin

http://www.medscape.com/viewarticle/735425

‘Bicycle Sign’ May Distinguish Parkinson’s From Atypical Parkinsonism
Susan Jeffrey
From Medscape Medical News > Neurology

January 7, 2011 — New research suggests the preserved ability to ride a bicycle after onset of symptoms may accurately differentiate between Parkinson’s disease (PD) and atypical parkinsonism.

The investigators, with senior study author Bastiaan R. Bloem, MD, PhD, medical director of the Parkinson Center Nijmegen at Radboud University Nijmegen Medical Center, the Netherlands, had previously reported a case study of a patient with advanced PD who showed an astonishing residual ability to ride a bicycle.

Now they have found in a new series of patients that preserved cycling ability is limited to patients with PD but is lost after disease onset among those with atypical parkinsonism.

“Simply asking about cycling abilities could be added to the list of red flags that can assist clinicians in their early differential diagnosis of parkinsonism,” the study authors conclude.

They report their findings as correspondence in the January 8 issue of The Lancet.

Freezing of Gait

In April 2010, Dr. Bloem and colleague Anke Snijder, MD, reported the case of a 58-year-old man with advanced PD and severe freezing of gait who could nonetheless ride his bicycle for up to 15 miles per day. After meeting this patient, Professor Bloem reported having found an additional 20 PD patients in his outpatient clinic, where he specializes in gait and balance disorders, all of whom could still ride a bicycle (N Engl J Med. 2010;362:13).

“In hindsight, it’s not a unique observation, and we’ve just missed out, maybe because we failed to ask about it or patients fail to volunteer this, but it’s certainly not a unique observation,” he told Medscape Medical News at that time.

Making the differential diagnosis between PD and atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy, or Lewy body dementia, is important clinically for counseling patients and accurate inclusion of suitable patients into trials but remains challenging, they note.

“Here, we suggest that the answer to 1 simple question — ‘Can you still ride a bicycle?” — offers good diagnostic value for separating Parkinson’s disease from atypical parkinsonism,” they write.

To look at this prospectively, investigators performed an observational study of 156 consecutive patients who presented with parkinsonism but did not yet have a definitive diagnosis. All had a structured interview, comprehensive neurological assessment, and cerebral magnetic resonance imaging (MRI) at baseline. Standard questions in the interview asked “whether, when, and why” cycling had become impossible for them.

The gold standard for diagnosis was at 3 years of follow-up, based on clinical examination, response to treatment, and MRI.

Of these patients, 111 had ridden a bicycle before first manifestation of their disease; 45 developed PD and 64 some form of atypical parkinsonism, mostly multiple system atrophy (n = 35, 31.5%) or vascular parkinsonism (n = 17, 15.3%).

At the time of inclusion in the study, occurring at a median disease duration of about 30 months, 34 of 64 patients ultimately diagnosed as having atypical parkinsonism had stopped cycling compared with only 2 of the 45 PD patients, yielding a sensitivity of 52%, and a specificity of 96% (area under the curve, 0.74; 95% confidence interval, 0.64 – 0.83).

The loss of cycling ability was seen with all atypical parkinsonism conditions, they note, and regression analysis showed no significant effect of age, parkinsonism, or ataxia on this ability, “suggesting this was an independent marker of atypical parkinsonism,” they write.

Cycling requires a highly coordinated interplay among balance, coordination, and rhythmic pedaling of the legs, Dr. Bloem and colleagues point out. “This skilled task is probably sensitive to subtle problems with balance or coordination, caused by the more extensive extranigral pathology in atypical parkinsonism,” they speculate.

“We suggest that loss of the ability to cycle after disease onset might serve as a new red flag, signaling the presence of atypical parkinsonism,” the study authors conclude. “The diagnostic value of the ‘bicycle sign’ was good: its presence was highly specific for the diagnosis of atypical parkinsonism.”

The study was supported by a research grant from the Internationaal Parkinson Fonds. The study authors have disclosed no relevant financial relationships.

Case Report of CBDer with Alien Hand Syndrome

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This article on alien hand syndrome is available at no charge online. See:

http://www.plosone.org/article/info%3Ad … ne.0015010

It contains an interesting case report of someone diagnosed clinically with CBD on the basis of alien hand syndrome and declining response to levodopa (Sinemet). The case report describes in great detail how the features of this patient’s alien hand.

I’ve copied the (understandable) introduction and case report below. Further down is the abstract.

Robin

Here are excerpts:

“The alien hand syndrome (AHS) is a very rare movement disorder. Patients with AHS experience one of their limbs as alien, which acts autonomously and performs meaningful movements without being guided by the intention of the patient. The patients find themselves unable to stop the alien hand from reaching and grabbing objects without using their other hand. Patients are aware that the limb is still part of their body, but they report the feeling as if an external agent is controlling the limb. Consequently, they often describe it in the third person.”

“The phenomenon of AHS is complex and has various clinical manifestations, possibly related to different lesion sites. … The neural mechanisms of this movement disorder still remain unclear. It has been proposed that unwanted movements may arise because of a release of the primary motor cortex (M1) from conscious control by intentional planning systems.”

“Here we report data of a patient diagnosed with corticobasal degeneration and left hand AHS. His left hand showed relatively preserved volitional motor functions. Although there were spontaneous movements of the alien hand, we also had the possibility to elicit alien movements of the hand in a controlled way. We were able to evoke movements of the hand by slightly pushing the hand away from the patient’s body, which then resulted in a small movement into the opposite direction. This behavior is also known as “Gegenarbeiten”, meaning counteracting or working against. Using this reliable behavioural effect we conducted a functional magnetic resonance imaging (fMRI) study to further examine the neural correlates of unconscious or alien movements.”

“The study consisted out of two fMRI experiments. We first examined unwanted movements the way described above. The second experiment was a motor localizer scan to assess brain areas associated with conscious movements.”

Case report
“The 75-year-old right-handed gentleman (WH) was diagnosed with Parkinson’s syndrome five years ago. Within the last six months he reported a rapid loss of control of his left hand. It became much more stiffed and lost fine motor skills. When he walked down a stair he was not able to release the railway voluntary. Playing table tennis became awful. He was not able to serve because the left hand did not loose the grip of the ball. Dopaminergic medication was not as efficient as it used to be at the beginning of disease.”

“Clinically we saw an uplifted arm and reduced arm swing on the left side, strongly left sided rigidity and intermitted irregular myoclonus of the left arm. There were no signs of sensory deficit; reflexes were obtained symmetrical. Tracer studies (DAT Scan and IBZM Spect) revealed loss of presynaptic dopamine as well as a reduction of the post-synaptic dopaminergic receptor state. Structural MRI showed increased and asymmetrical ventricles. Based on the clinic and imaging we diagnosed an atypical Parkinsonian syndrome by possible corticobasal degeneration.”

“After increasing of dopaminergic medication rigidity improved but by now WH reported attacks of his left hand toward his body: the hand grabbed into his face and he could not loose the grip voluntary. When he used his right hand to release the left hand from his face the grip of the left hand became even stronger and he got scratched. He then controlled his hand during night covering up the left arm and keeping the bedside lamp turned on. Neuropsychological testing revealed intermanual conflict (the left hand did not let go objects), transitive dyspraxia using an object (i.e. hole-puncher), only slightly reduced tactile sensory, and tonic grasping. No mirror movements or synkinesis was observed.”

Here’s the abstract:

PLoS One. 2010 Dec 13;5(12):e15010.

Alien Hand Syndrome: Neural Correlates of Movements without Conscious Will.

Schaefer M, Heinze HJ, Galazky I.
Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.

Abstract
BACKGROUND: The alien hand syndrome is a striking phenomenon characterized by purposeful and autonomous movements that are not voluntarily initiated. This study aimed to examine neural correlates of this rare neurological disorder in a patient with corticobasal degeneration and alien hand syndrome of the left hand.

METHODOLOGY/PRINCIPAL FINDINGS: We employed functional magnetic resonance imaging to investigate brain responses associated with unwanted movements in a case study. Results revealed that alien hand movements involved a network of brain activations including the primary motor cortex, premotor cortex, precuneus, and right inferior frontal gyrus. Conscious and voluntary movements of the alien hand elicited a similar network of brain responses but lacked an activation of the inferior frontal gyrus. The results demonstrate that alien and unwanted movements may engage similar brain networks than voluntary movements, but also imply different functional contributions of prefrontal areas. Since the inferior frontal gyrus was uniquely activated during alien movements, the results provide further support for a specific role of this brain region in inhibitory control over involuntary motor responses.

CONCLUSIONS/SIGNIFICANCE: We discuss the outcome of this study as providing evidence for a distributed neural network associated with unwanted movements in alien hand syndrome, including brain regions known to be related to movement execution and planning as well as areas that have been linked to inhibition control (inferior frontal gyrus) and experience of agency (precuneus).

PMID: 21179436

Primary Progressive Aphasia- Notes from Weintraub Talk

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There was a conference call today for support group leaders put on by the Association for Frontotemporal Dementias. (PSP and CBS/CBD fall into the “movement disorders” type of FTDs, which is how/why I’m invited to attend.) The topic of the call was Primary Progressive Aphasia, and the speaker was Sandy Weintraub, PhD, of Northwestern, one of the centers in the US studying PPA (and all FTDs).

My notes are below.

Robin

FYI – PPA has been addressed briefly in two webinars this year:

Boeve Webinar: Dr. Weintraub’s presentation is an expansion of the PPA topic within Dr. Brad Boeve’s recent webinar on cognitive and behavioral aspects in FTDs. Dr. Boeve said taht 60% of those with a clinical diagnosis of PPA end up being diagnosed with a tauopathy (such as PSP, CBD, or AD) upon brain autopsy.

I posted my notes on Dr. Boeve’s webinar back in April 2010:
http://forum.psp.org/viewtopic.php?t=8410

Litvan Webinar: As we learned in Dr. Irene Litvan’s presentation, one of the three clinical presentations of CBS is PPA. In my notes on Dr. Litvan’s presentation, I had complained that she hadn’t covered the “progressive aphasia” presentation at all. Well, today’s conference call certainly supplied the missing pieces.

I posted my notes on Dr. Litvan’s webinar back in October 2010:
http://forum.psp.org/viewtopic.php?t=8575

FTD Support Group Leaders’ Conference Call
Organizer: Association for Frontotemporal Dementias (ftd-picks.org)
12/20/10

Topic: Primary Progressive Aphasia: Understanding language presentations and approaches to care

Speaker: Sandra Weintraub, PhD
Northwestern University’s CNADC (Cognitive Neurology and Alzheimer’s Disease Center)
Chicago, IL
www.brain.northwestern.edu/ppa/

The FTD class of disorders is ever-widening.

Three main types of FTD disorders, depending on early symptoms:
* change in behavior, personality, and emotions: bvFTD
* decline in language (speaking, understanding, reading, writing): PPA
* change in motor function and movement: PSP, CBS, MND

“Early” = first 2 years. These years are critical for families. And critical for clinicians to understand the underlying pathology.

PSP, CBS, and MND often have cognitive symptoms associated with them as they progress.

All FTD disorders are progressive.

What is aphasia?
1. A disorder of language: inability to link words to thoughts for communication
2. Caused by brain damage: usually associated with a sudden loss of language function, caused by a stroke but in PPA is slowly progressive because the cause is neurodegenerative disease
3. Affects all aspects of language usage, not just speech output. A disorder of speech alone without language
impairment is “dysarthria” and it does not prevent the individual from communicating their thoughts since they can
still write normally. Asking the patient to write is one way to distinguish aphasia and dysarthria.

Early Symptoms of PPA (Primary Progressive Aphasia)
1. Gradual loss of language (aphasia): word-finding, speaking in full sentences, understanding conversation and/or written words, writing.

Subtypes include: Agrammatic, Logopenic, Semantic. Subtype depends on what the language disorder is.
Agrammatic: They say “water” rather than “I want water now.”
Logopenic: Slow output and groping for words.
Semantic: What is “salt”? Single-word comprehension deficit. (Called “Semantic Dementia”.)

2. Other cognitive functions are normal or relatively so. Hard to test someone’s memory if they can’t speak.

3. Daily living activities are affected mostly by aphasia in early stages. This is because short term memory and personality are intact.

4. Aware of symptoms and can become depressed due to this awareness.

5. Symptoms progress over time and other problems develop.

Boston Naming Test is used in diagnosis.

Example – Pictures of objects. The patient is asked to name the object.

Example – Test of single word comprehension – nouns and verbs. “Show me the picture where someone is laughing.” Someone with Semantic subtype cannot do.

Example – Color name comprehension. “Show me the color blue.”

Example – Body part name comprehension. “Show me the nose.”

“My sister like to have wheat bread. She will puts the mayo, cheese, turkey and lettuce. She will take a knife to cut the sandwich. The sandwich will put on the plate, My sister will have milk in a glass.”

–> This is agrammatic

“Get whatever type of bread you would like. Then add cheese, with different types. Then add liquid on the bread. Then leados, vegitables, chicken or turkey or other different ones. Then you have a good one!”

–> Fewer nouns here. The patient is having difficulty coming up with the right words. Could be agrammatic, logopenic or semantic! Lots of overlap! She thinks it is a logopenic patient. (I think “leados” is “lettuce.”)

MRI scan on the left. (Taken as if you were standing above the patient’s head.) PET scan on the right. The left side of the images are the right side of the brain.

Later Symptoms:
1. Mutism. Usually this is a late symptom. In rare cases, someone can be mute for 3-4 years.
2. Severe difficulty understanding what others are saying even though hearing is normal
3. Personality changes
4. Memory loss
5. Daily living activities severely limited

Early PPA vs. bvFTD:
PPA patients have aphasia but no other symptoms.
bvFTD patients have personality change, concentration problem, and social-interpersonal problems.
Motor symptoms may be present in both.

Late PPA vs. bvFTD:
PPA patients have aphasia and concentration problem. They may or may not have memory loss, visual disorder, personality change, and social-interpersonal.
bvFTD patients have personality change, concentration problem, and social-interpersonal problems. They may or may not have aphasia, memory loss, and visual disorder.
Motor symptoms may be present in both.

Visual disorder = your brain can’t see.

bvFTD and PPA
* Psychosocial and treatment strategies differ vastly from memory loss dementia.
* Need specialized education, support services, community resources.

Northwestern’s PPA/FTD Program
* website: brain.northwestern.edu/ppa/
* semi-annual newsletters to NWU patients and families
* monthly caregiver support groups. They’ve been asked to split these into two — PPA and bvFTD.
* one conference per year (caregivers and patients)

In the new FTD booklet, there’s a section on PPA:
www.nia.nih.gov/Alzheimers/Publications/FTLD/

Strategies for families in managing symptoms of aphasia:
* Speak in simple sentences to patients — simpler words and simple forms of construction. Don’t use the word “or”!
* Construct a communication notebook for patients. Have a page devoted to “my favorite grocery items.” Take pictures and label them with words. iPhone application says words aloud.
* Devise a strategy for emergency situations bypassing the need to use the telephone
* Seek treatment from a speech-language pathologist
* Provide patient with identifying information, Example – MedicAlert bracelets.
* These are from: Weintraub S, Morhardt DJ: Treatment, education and resources for non Alzheimer dementia: One size does not fit all. Alzheimer’s Care Quarterly, July/September: 201-214, 2005. They are summarized in one of the handouts we received.

Question & Answer:

Q: What about the patient who lives alone?

A: Though some of these patients can’t speak, they may still be highly functional. Need to assess how this person can react to an emergency.

Q: What about depression?

A: This can be a serious problem. Medications can be very helpful. Families should be on the look-out for this.

Talking therapy is not always the best thing!

Comment by audience member: There can be profound loneliness in PPA.

Q: Any learnings from your patient support group?

A: Keep gatherings small. More like one-on-one or two-on-one. Any more people gets confusing for the patient.

Q: How does your patient support group work?

A: The patients demanded their own support group. Over time, the amount of talking has declined. Group leaders now insert activities when there isn’t much talking.

Q: What percentage of PPA patients end up having personality involvement?

A: We don’t know. All of the research has been with small series of patients.

Some studies show that the Semantic patients end up with more emotional/behavioral disturbances. This may be due to frontal lobe involvement.

Q: Is Namenda helpful in PPA?

A: Namenda didn’t help with PPA in a trial they did (3-6 months). There was no short-term benefit. So they assumed there was no long-term benefit.

Comment by audience member: Namenda helped his wife for several years.

Q: What portion of FTDs are PPA?

A: We don’t know. Northwestern sees a huge number of PPA patients.

Q: What do we know about genetic patterns with PPA?

A: There are only two PPA families we know of where it seems to be inherited.

In families, where someone has PPA, other family members (first degree relatives) may have early learning disorders (eg, dyslexia).

We haven’t followed those with early learning/language disorders to find out if they develop neurodegenerative diseases later.

Q: What are the pathological diagnoses for PPA?

A: We do have data on this:

60% of all PPA have some form of FTLD pathology (whether it’s tauopathy, FTDP43, CBD, PSP, etc).

40% have Alzheimer’s pathology.

If you have the logopenic form of PPA, you are more likely to have the Alzheimer’s form.

If you have the grammar form of PPA, you are more likely to have a tauopathy.

24 Mayo Patients with CBS Diagnoses

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This is a newly-published Mayo Rochester study of 24 patients with a clinical diagnosis of CBS (corticobasal syndrome) who had undergone MRI during life and donated their brains upon death. These 24 patients had these pathologic diagnoses:

7 had CBD
6 had PSP
6 had AD (Alzheimer’s Disease)
5 had FTLD with TDP-43

29% were diagnosed accurately during life. 54% were diagnosed accurately during life if you include the PSP diagnoses. (As PSP and CBS/CBD are treated similarly and are both tauopathies, I’m willing to consider PSP a correct diagnosis. Many of you will not agree.)

Indeed, in our local support group, several diagnosed while alive with CBS/CBD turned out to have had PSP. And there are many on the CBD-related Yahoo!Group who report that their family members were diagnosed during life with CBS/CBD but upon death with AD.

The researchers then looked at the previous MRI scans to “determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS.” They found:

“Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology.”

It’s a nice study. Wish it could’ve been with more than 24 patients.

Robin

Neurology. 2010 Nov 23;75(21):1879-87.

Imaging correlates of pathology in corticobasal syndrome.

Whitwell JL, Jack CR Jr, Boeve BF, Parisi JE, Ahlskog JE, Drubach DA, Senjem ML, Knopman DS, Petersen RC, Dickson DW, Josephs KA.
Department of Radiology, 200 1st Street SW, Rochester, MN.

Abstract
BACKGROUND: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS.

METHODS: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls.

RESULTS: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD.

CONCLUSIONS: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology.

PubMed ID#: 21098403

Excerpt from PSP/CBD Guide on Sinemet

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Several medications, all available only by prescription, can help PSP in some cases.

• Sinemet
This is the brand name for a combination of levodopa and carbidopa. Levodopa is the component that helps the disease symptoms. Carbidopa simply helps prevent the nausea that levodopa alone can cause. When levodopa came along in the late 1960’s, it was a revolutionary advance for Parkinson’s but, unfortunately, it is of only modest benefit in PSP. It can help the slowness, stiffness and balance problems of PSP to a degree, but usually not the mental, speech, visual, or swallowing difficulties. It usually loses its benefit after two or three years, but a few patients with PSP never fully lose their responsiveness to Sinemet.

Some patients with PSP require large dosages, up to 1,500 milligrams (mg.) of levodopa as Sinemet per day to see an improvement, so the dosage should be pushed to at least that level, under the close supervision of a physician, unless a benefit or intolerable side effects occur sooner. The most common side effects of Sinemet in patients with PSP are confusion, hallucinations and dizziness. These generally disappear after the drug is stopped. The most common side effect in patients with Parkinson’s disease, involuntary writhing movements “chorea” or dyskinesias) occur very rarely in PSP, even at high Sinemet dosages.

Patients with PSP should generally receive the standard Sinemet (or generic levodopa/carbidopa) preparation rather than the controlled-release (Sinemet CR or generic levodopa/carbidopa ER) form. The CR form is absorbed from the intestine into the blood slowly and can be useful for people with Parkinson’s disease who respond well to Sinemet but need to prolong the number of hours of benefit from each dose. In PSP, however, such response fluctuations almost never occur. Because Sinemet CR is sometimes absorbed very little or erratically, a poor CR response in a patient with PSP might be incorrectly blamed on the fact that the disease is usually unresponsive to the drug. Such a patient might actually respond to the standard form, which reaches the brain in a more predictable way.

A new formulation of levodopa-carbidopa is Parcopa, which dissolves under the tongue. For people with PSP who cannot swallow medication safely, this could be useful. Another approach for such patients is to crush a regular levodopa-carbidopa tablet into a food or beverage that is easily swallowed. Another new formulation of levodopa-carbidopa (called Stalevo) combines those two drugs with a third drug, entacapone, in the same tablet. The entacapone slows the rate at which dopamine is broken down. It is useful for patients with Parkinson’s whose levodopa-carbidopa works well but only for a few hours per dose. This situation rarely, if ever, occurs in PSP.