Category Archives: CBD

Hallucinations – rare in PSP and CBD

Date
Posted by

The authors review the prevalence of and treatment options for hallucinations in Progressive Supranuclear Palsy, Corticobasal Degeneration, and many other disorders. “Overall hallucinations are a rare symptom in PSP and CBD. However, if reported, VH [visual hallucinations] predominate. Questionnaire-based studies found hallucinations in 5–13% in PSP and in 5–21% in CBD. This was echoed by two autopsy-based studies with retrospective chart review where the prevalence was 7% for PSP and 0% for CBD.”

The authors argue that because of the need for treatment, “the distinction of disease-inherent hallucinations from medication-associated perceptual disturbances is highly relevant.” This article addressed medication-associated hallucinations along with delirium-associated hallucinations and surgery-associated hallucinations. Both delirium- and surgery-associated hallucinations may be due to medication as well.

I’ve copied the abstract of the article below.

Robin

CNS Neuroscience & Therapeutics. 2011 Feb 16. [Epub ahead of print]

Hallucinations in Neurodegenerative Diseases.

Burghaus L, Eggers C, Timmermann L, Fink GR, Diederich NJ.
Department of Neurology, University of Cologne, Cologne, Germany Cognitive Neurology Section, Institute of Neurosciences and Medicine (INM3), Research Center Jülich, Jülich, Germany Department of Neurology, Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.

Abstract
Background: Patients with neurodegenerative disease frequently experience hallucinations and illusionary perceptions. As early symptoms, hallucinations may even have diagnostic relevance (i.e., for the diagnosis of Lewy Body Dementia).

In the later course of the disease, hallucinations may appear as characteristic symptoms and often constitute a particular challenge for therapeutic endeavors.

Here, the distinction of disease-inherent hallucinations from medication-associated perceptual disturbances is particularly relevant.

Results: Synucleinopathies and tauopathies have different risk profiles for hallucinations. In synucleinopathies hallucinations are much more frequent and phenomenology is characterized by visual, short-lived hallucinations, with insight preserved for a long time. A “double hit” theory proposes that dysfunctionality of both associative visual areas and changes of limbic areas or the ventral striatum are required.

In contrast, in tauopathies the hallucinations are more rare and mostly embedded in confusional states with agitation and with poorly defined or rapidly changing paranoia. The occurrence of hallucinations has even been proposed as an exclusion criterion for tauopathies with Parkinsonian features such as progressive supranuclear palsy.

Conclusion: To date, treatment remains largely empirical, except the use of clozapine and cholinesterase inhibitors in synucleinopathies, which is evidence-based. The risk of increased neuroleptic sensitivity further restricts the treatment options in patients with Lewy Body Dementia. Coping Strategies and improvement of visual acuity and sleep quality may be useful therapeutic complements.

© 2011 Blackwell Publishing Ltd.

PubMed ID#: 21592320 (see pubmed.gov for this abstract only)

“New insights” into CBD

Date
Posted by

This recently-published paper is about “new insights” into atypical parkinsonism, including MSA, DLB, PSP, and CBD. The paper is based upon medical journal articles published in 2010. Two of the three authors are well-known Austrian researchers in the atypical parkinsonism community.

The authors describe atypical parkinsonian disorders (APDs) as “characterized by relentlessly progressive and levodopa refractory parkinsonism associated with a range of distinctive atypical features.”

Here are the key points made in the article related to CBD:

* “The clinical presentation of CBD is variable and includes the CBS, PSP, progressive aphasia, and frontotemporal dementia. However, CBD research is hampered by the rarity of the disorder, patients being scattered over a large geographic area.”

* “A recent clinicopathological study showed that only the minority of postmortem confirmed CBD cases were diagnosed correctly in life (five out of 19 cases) and that the clinical syndrome of CBS is not specific for CBD. Intriguingly, most of the pathologically confirmed CBD cases were characterized clinically by a PSP-like presentation with delayed onset of vertical supranuclear gaze palsy.”

* “Intriguingly, an Alzheimer’s disease-like CSF pattern was associated with early memory decline in patients with CBS according to a recent study.”

Copied below is the abstract.

Robin

Current Opinion in Neurology. 2011 May 13. [Epub ahead of print]

New insights into atypical parkinsonism.

Wenning GK, Krismer F, Poewe W.
Department of Neurology, Medical University, Innsbruck, Austria.

Abstract

PURPOSE OF REVIEW:
Atypical parkinsonian disorders (APDs) comprise a heterogenous group of disorders including multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Based on literature published in 2010, we here review recent advances in the APD field.

RECENT FINDINGS:
Genome-wide association studies have provided robust evidence of increased disease risk conferred by synuclein and tau gene variants in MSA and PSP. Furthermore, advanced imaging tools have been established in the differential diagnosis and as surrogate markers of disease activity in patients with APDs. Finally, although therapeutic options are still disappointing, translational research into disease-modifying strategies has accelerated with the increasing availability of transgenic animal models, particularly for MSA.

SUMMARY:
Remarkable progress has been achieved in the field of APDs, and advances in the genetics, molecular biology and neuroimaging of these disorders will continue to facilitate intensified clinical trial activity.

PubMed ID#: 21577106 (see pubmed.gov for this abstract only)

Review of CBD (Mayo)

Date
Posted by

Mayo researchers just published an article on CBD. The abstract is a mix of clinical information and pathological information. If you are like me, you’ll want to skip past the pathological terminology!

The clinical information in the abstract leads me to believe that the article’s content is very similar to Dr. Irene Litvan’s webinar several months ago on CBD. You can find my notes on that webinar here:

http://forum.psp.org/viewtopic.php?t=8575

The abstract mentions the term “Richardson syndrome.” This refers to the most common form of PSP (progressive supranuclear palsy); one of the symptoms of this form is cognitive impairment.

Robin

Nature Reviews. Neurology. 2011 Apr 12. [Epub ahead of print]

Corticobasal degeneration: a pathologically distinct 4R tauopathy.

Kouri N, Whitwell JL, Josephs KA, Rademakers R, Dickson DW.
Department of Neuroscience Mayo Clinic, Jacksonville, FL.

Abstract
Corticobasal degeneration (CBD) is a rare, progressive neurodegenerative disorder with onset in the 5(th) to 7(th) decade of life. It is associated with heterogeneous motor, sensory, behavioral and cognitive symptoms, which make its diagnosis difficult in a living patient.

The etiology of CBD is unknown; however, neuropathological and genetic evidence supports a pathogenetic role for microtubule-associated protein tau.

CBD pathology is characterized by circumscribed cortical atrophy with spongiosis and ballooned neurons; the distribution of these changes dictates the patient’s clinical presentation. Neuronal and glial tau pathology is extensive in gray and white matter of the cortex, basal ganglia, diencephalon and rostral brainstem. Abnormal tau accumulation within astrocytes forms pathognomonic astrocytic plaques.

The classic clinical presentation, termed corticobasal syndrome (CBS), comprises asymmetric progressive rigidity and apraxia with limb dystonia and myoclonus. CBS also occurs in conjunction with other diseases, including Alzheimer disease and progressive supranuclear palsy.

Moreover, the pathology of CBD is associated with clinical presentations other than CBS, including Richardson syndrome, behavioral variant frontotemporal dementia, primary progressive aphasia and posterior cortical syndrome.

Progress in biomarker development to differentiate CBD from other disorders has been slow, but is essential in improving diagnosis and in development of disease-modifying therapies.

PubMed ID#: 21487420 (see pubmed.gov for this abstract only)

Adjusting to the diagnosis – 4/6/11 webinar notes

Date
Posted by

If anyone else attended this webinar today, I’d be interested in receiving your comments and any notes you took (especially in places where I missed things). I thought the middle part of the webinar was especially good. If you missed it, here are my notes. And CurePSP staff indicated that the recording of this webinar should be available online (psp.org) by 4/8/11.

Early Stages of Diagnosis: A Family Guide for PSP, CBD & MSA — the process of adjusting to the diagnosis, and important steps for patients and families to take during the early stages of the diseases

Webinar Speaker: Trish Caruana, MSW, VP of Programs and Education at CurePSP

4/6/11 (rescheduled to this day from 3/30)

Objectives
* Provide a brief overview of PSP, CBD, and MSA
* Discuss the process of being diagnosed
* Review the initial adjustment to the diagnosis
* Outline the steps to take to ensure the best overall care
* Develop a framework to maintain health

What is PSP?
* Rare neurodegenerative brain disease (5-6 per 100K – “incidence.” Robin’s note: she means “prevalence”)
* Problems with stiffness, balance and vision, speech and swallowing
* Changes in personality
* Cognitive changes

What is CBD?
* Similar to PSP (balance, vision, speech and swallowing)
* Rare: estimated 2K-3K in the US
* Difficulty generating and articulating speech
* Stiffness, jerkiness, slowness, and clumsiness either in the upper or lower extremities
* Asymmetric onset of symptoms
* Memory or behavior problems
* Many of these symptoms may not be appearing now, if you are in the early diagnosis phase

What is MSA:
* Also an atypical parkinsonian disease
* Involuntary functions are affected such as blood pressure, heart rate, actions of the intestines and bladder and breathing activity
* OH
* Urinary incontinence and constipation
* Impaired speech and swallowing
* Inability to sweat
* Sleep apnea and sleep disturbance
* Waving hand movements and staggering gait

Someone initially given this info is going to be taking in a lot of info and trying to figure out how their lives will change.

The process of being diagnosed
Buddhist saying: “If you are facing the right direction, all you need to do is keep walking.”
Getting a diagnosis affects everyone psychologically

Misconceptions about diagnosis
Our simplistic view: Symptoms + Evaluation = Diagnosis

Finding out what’s really going wrong
Medical response: Evaluation; treating symptoms; referrals to other specialists; new and worsening symtoms; no diagnosis given; some diagnosis given; correct diagnosis
Patient and family reactions: Hope for answers; poor response to treatments; frustration; fear; confusion; the power of “naming”; disbelief; panic (what can we do? what info is there? assumption is often that there is one thing that can be done)

Initial adjustments to the diagnosis on the part of the patient and family:
* intellectual (making sense of info; paring down the info)
* physical (probably the patient has already made physical adjustments to the falls, for example)
* psychological (our sense of who we are)
* emotional (people feel that the illness defines them)
* social (people may drop out of activities they enjoy due to fatigue or depression)
* financial (healthcare costs, job, career, retirement)
* life plans (what were my future plans? time for reassessment of these plans)
* spiritual/religious

It’s natural for patients to think about many of these things on their own. We hope they have a good support system.

It’s natural for people to question the diagnosis.

After diagnosis: denial, anger, bargaining, depression, acceptance
These are the five stages of grief (and dealing with loss) by Elizabeth Kubler-Ross

The most important thing about acceptance is that it can lead to taking action. Taking action has four components:
1- Education: disease; current treatment; research; organizations; experts. (“Can’t take action until you know these things.”)
2- Medical: neurologist; movement disorder specialists (“usually this is a neurologist but sometimes it can be a psychologist or nurse practitioner.” Robin’s note – a psychologist cannot be a movement disorder specialist!); primary care physician (who can “synthesize info”); rehab specialists; study sites
3- Resources (“information in the community that may be helpful”): organizations (including Parkinson’s Disease support groups); adaptive equipment; home health; transportation
4- Social Supports: family; extended family; friends; colleagues; church/synagogue; support groups

Creating a framework for maintaining the best health possible for yourself and your family

Continuing to move forward if you have the disease:
* Ask for help from medical providers. Come prepared to appointments with your questions.
* Acknowledge and accept your own thoughts and feelings
* Share your concerns and emotions with someone close to you
* Consider professional counseling/group support
* Ask for help from your family and friends
* Stay in touch with people you love and help them understand the disease
* Remember what helped you cope with other difficult situations in your life and draw from those experiences
* Maintain daily routines as much as possible
* Enjoy the simple things
* Focus on what you can control
* Find courage and direction in your faith or belief system

If your loved one has the disease:
* Recognize it’s normal to feel a variety of emotions
* Maintain and/or start new routines that promote your physical and mental health. Don’t get out of balance by spending 7×24 with your family member with the disease.
* Create a support system
* Continue to learn as much as you can — connect with others going through the challenges of the disease and share ideas
* Accept that you are human

CurePSP can help
* Visit our website
* Request or download our educational materials
* Read our newsletters (Robin’s note: I have not seen a CurePSP newsletter in perhaps a year. Even the old issues are no longer posted on the CurePSP website.)
* Listen to our ongoing webinars
* Attend our family conferences
* Contact us

Question & Answer Period: (all answers are given by Trish)

Robin’s Comment: The #s are prevalence numbers, not incidence #s.

Trish’s Reply: We don’t have good numbers on these diseases. Hopefully our numbers will improve with research.

Robin’s Comment: Perhaps you can address denial. Many caregivers comment that their family members are in denial. Is this a problem?

Trish’s Reply: It’s a defense mechanism. It can serve a good purpose. It can be seen as a stubbornness to stay involved in life. But it can also lead people to think that they don’t need help, and they aren’t open to talking.

Never advisable to take someone’s defense mechanism away unless you have something equally effective to substitute for it.

Question: To what extent are medical students exposed to these diseases?

Answer: When PD is mentioned in the curriculum, it gets short shrift. Therefore, one can imagine that these diseases, as a subset, are not well-covered. It would be hard to find people to interview with the disease.

Comment: PT is helpful.

Trish’s Comment: CurePSP is doing some advocacy to help insure that PT is covered over the course of the disease.

Question: Husband with CBD has depression but isn’t taking anti-depressant.

Answer: Medication can make symptoms worse and can have side effects. Even a positive reaction can be short-lived. Hopefully a decision about taking an anti-depressant is made with a neurologist or psychiatrist. There are many kinds of anti-depressants. Raise this issue with the care provider. Perhaps ask for a psychiatry referral.

Question: What about erratic behaviors?

Answer: People can be impulsive. Example: someone with gait problems but they get up to walk on their own. No one way to help with these impulsive behaviors.

Try to assess whether there are times that make these behaviors worse. Then come up with a plan for the person.

Neurodegenerative disease misclassified as psychiatric

Date
Posted by

This UCSF study says more about the behavioral variant of frontotemporal dementia than it does about PSP, CBD, or the other neurodegenerative diseases included in the research. The researchers’ conclusion makes a couple of points:

* “Neurodegenerative disease is often misclassified as psychiatric disease. …[When] patients with neurodegenerative disease are initially classified with psychiatric disease, the patient may receive delayed, inappropriate treatment and be subject to increased distress.”

* “Physicians should consider referring mid- to late-life patients with new-onset neuropsychiatric symptoms for neurodegenerative disease evaluation.”

Robin

Journal of Clinical Psychiatry. 2011 Feb;72(2):126-33.

The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease.

Woolley JD, Khan BK, Murthy NK, Miller BL, Rankin KP.
UCSF, San Francisco, CA.

Abstract
OBJECTIVE: To identify rates of and risk factors for psychiatric diagnosis preceding the diagnosis of neurodegenerative disease.

METHOD: Systematic, retrospective, blinded chart review was performed of 252 patients with a neurodegenerative disease diagnosis seen in our specialty clinic between 1999 and 2008.

Neurodegenerative disease diagnoses included
* behavioral-variant frontotemporal dementia (n = 69),
* semantic dementia (n = 41), and
* progressive nonfluent aphasia (n = 17) (all meeting Neary research criteria);
* Alzheimer’s disease (n = 65) (National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association research criteria);
* corticobasal degeneration (n = 25) (Boxer research criteria);
* progressive supranuclear palsy (n = 15) (Litvan research criteria); and
* amyotrophic lateral sclerosis (n = 20) (El Escorial research criteria).

Reviewers remained blinded to each patient’s final neurodegenerative disease diagnosis while reviewing charts. Extensive caregiver interviews were conducted to ensure accurate and reliable diagnostic histories. For each patient, we recorded history of psychiatric diagnosis, family psychiatric and neurologic history, age at symptom onset, and demographic information.

RESULTS: A total of 28.2% of patients with a neurodegenerative disease received a prior psychiatric diagnosis. Depression was the most common psychiatric diagnosis in all groups.

Behavioral-variant frontotemporal dementia patients received a prior psychiatric diagnosis significantly more often (50.7%; P < .001) than patients with Alzheimer’s disease (23.1%), semantic dementia (24.4%), or progressive nonfluent aphasia (11.8%) and were more likely to receive diagnoses of bipolar disorder or schizophrenia than were patients with other neurodegenerative diseases (P < .001). Younger age (P < .001), higher education (P < .05), and a family history of psychiatric illness (P < .05) increased the rate of prior psychiatric diagnosis in patients with behavioral-variant frontotemporal dementia.

Cognitive, behavioral, and emotional characteristics did not distinguish patients who did or did not receive a prior psychiatric diagnosis.

CONCLUSIONS: Neurodegenerative disease is often misclassified as psychiatric disease, with behavioral-variant frontotemporal dementia patients at highest risk.

While this study cannot rule out the possibility that psychiatric disease is an independent risk factor for neurodegenerative disease, when patients with neurodegenerative disease are initially classified with psychiatric disease, the patient may receive delayed, inappropriate treatment and be subject to increased distress.

Physicians should consider referring mid- to late-life patients with new-onset neuropsychiatric symptoms for neurodegenerative disease evaluation.

© Copyright 2011 Physicians Postgraduate Press, Inc.

PubMed ID#: 21382304