Educational video for neurologists – diagnosing (mostly) and treating PSP, CBS, MSA, and DLB

This 60-minute video was put together by CurePSP with the main goal to educate general neurologists on differentiating Parkinson’s Disease from the four atypical parkinsonism disorders – PSP, CBD, MSA, and DLB.  A CurePSP letter with a link to the YouTube video was sent out to 14,000 general neurologists in the US in May 2016.  Though the YouTube video was produced for neurologists, I found it understandable and think most of you will as well.

If you are seeing a general neurologist — not a movement disorder specialist and not a dementia specialist — my suggestion and request is that you share this email with the general neurologist.  Encourage him/her to spend 60 minutes to gain some additional info on diagnosis, evaluation, pathology treatment, care pathology, and prognosis of the four atypical parkinsonism disorders.

Be sure to explain to your general neurologist the resources and services of Brain Support Network — we have local support group meetings in Northern California, email lists focused on the atypical parkinsonism disorders, and that we help people nationally with all neurodegenerative diseases with brain donation.

For everyone viewing this post, my suggestion is that you skip to the last ten minutes of the video and listen starting with the medication management section.  Most of you are beyond the diagnosis so reading about the symptoms, how to diagnose, imaging, and the pathology is probably less interesting.

This video is a great service to general neurologists.  And probably primary care physicians and other healthcare professionals as well.  It’s unfortunate that the four atypical parkinsonism disorders are compared to Parkinson’s Disease ONLY but that is the context of this educational video.  It was made by movement disorder specialists.  As a point of reference, no one would’ve thought my father had Parkinson’s Disease.  Alzheimer’s Disease seemed far more likely in his case but a video that compares PSP to Alzheimer’s ONLY wouldn’t be 100% right either.  We need better “blending” of the movement disorder communities and the memory disorder communities!

I’ve copied below some notes on the 60-minute educational video.  This is definitely not a transcript.  In many places, I say “see slide.”  But the notes at least give you the time markers and some idea of what is discussed at certain times.

By the way, I’ve heard great things about Dr. Stephen Reich, the main speaker in the video.  He’s been part of the PSP/CBD community for many years.  One of the other authors of the educational presentation is Dr. Alexander Pantelyat, a movement disorder specialist from Johns Hopkins I’ve had the pleasure of meeting at conferences.  The third author of the presentation is Dr. Shawn Smyth, who shares some helpful videos of specific symptoms as part of this larger video.

If you learn anything, let me know!  Or, if your general neurologist wants to know more about any of these disorders or get involved with Brain Support Network, let me know!

Robin



www.youtube.com/watch?v=BtEiNlivgeI

Atypical Parkinsonian Disorders
60-minute tutorial for general neurologists
Produced by CurePSP, May 2016

Slide set put together by:
Stephen Reich, MD, University of Maryland
Shawn Smyth, MD, Parkinson’s and Movement Disorders Center of Maryland and Johns Hopkins University
Alexander Pantelyat, MD, Johns Hopkins

DIAGNOSIS

The importance of a correct diagnosis:
* avoiding repeated consultations, testing, and/or hospitalizations
* avoiding unnecessary diagnostic testing
* providing accurate prognostic information
* directing patients and families to appropriate resources/networking/clinical trials
* trying treatment strategies/care that may provide helpful

Parkinsonism is NOT Parkinson disease
* ParkinsonISM is a general term to describe movement (motor) problems that commonly appear together in certain illnesses
* The term parkinsonism comes from Parkinson’s disease, but these problems are also seen in other disordres
* The four main motor symptoms of parkinsonism: bradykinesia (slowness of movement), rigidity, tremor (rest), postural instability and gait dysfunction.
* Not everyone with parkinsonism has Parkinson’s disease though the majority do.

Differential diagnosis of parkinsonism in a flow diagram:
* 80% have primary parkinsonism or degenerative disease.  This breaks down as Parkinson’s disease (majority), atypical parkinsonian disorders, and heredo-degenerative parkinsonian disorders.
* 20% have secondary parkinsonism.  This breaks down as other brain conditions — vascular, hydroencephalic, infectious, traumatic, etc — or systemic etiologies — hypothyroidism, meds, toxins, etc.

(4:38) Degenerative causes of parkinsonism

More common presentations:
* Parkinson disease
* Atypical parkinsonian disorders
– progressive supranuclear palsy
– multiple system atrophy
– corticobasal syndrome
– dementia with Lewy bodies/diffuse Lewy body disease

Rarer presentations:  (this isn’t a complete list)
* frontotemporal dementia with parkinsonism (FTD-P)
* Alzheimer disease
* spinocerebellar ataxias (SCAs, often types 2, 3, 17)
* basal ganglia calcification (sporadic and inherited)
* Huntington’s disease (juvenile presentation)+
* Wilson disease (<50 years old)+
* acquired hepatolenticular degeneration

+ often have parkinsonism, dystonia, and tremor

Up to 25% of those who were thought to have Parkinson’s disease upon autopsy were found to have an alternative diagnosis.  The most common alternative diagnosis is another form of parkinsonism.  The most common of these are PSP, MSA, CBS, or DLB.

Degenerative parkinsonism and accumulating intracellular proteins
Synuclein:
* In Lewy bodies: PD and DLBD
* In glial cytoplasmic inclusions (GCIs): MSA
Tau:
* PSP, CBD, FTDP-17, Parkinson dementia complex of Guam

Secondary causes of parkinsonism
* Vascular: lower-half (waist down) parkinsonism; multi-infarct state; TIA history; step-wise progression; MRI scan indicative
* Hydrocephalus
* Space-occupying mass/lesion
* Endocrine (hypothryoid slowness)
* Toxic: manganese, carbon monoxide, cyanide, MPTP, carbon disulfide
* Drug-induced:  dopamine-receptor blockers (first and second generation antipsychotics; antiemetics, including Reglan); anticonvulsants/mood stabilizers (valproic acid, lithium); antiarrhythmics (amiodarone).  Most important category here.  Physicians are not very good at recognizing drug-induced parkinsonism.  This can last for a number of months, even a year, after the drug has been stopped.  It’s important to take a good drug history.
* Post-encephalitic
* Post-traumatic

(8:15) Steps to making a diagnosis
(See the slide)

Usually on PD and CBS are asymmetric.

Are there any symptoms that don’t fit with Parkinson’s?

Very important to take a careful drug history.

Atypical parkinsonian syndromes don’t respond at all to levodopa or have a short-lived response.  In PD, we are reassured that there’s a sustained response to levodopa over five years and when the patient develops dyskinesia.

(10:18) Dementia is typically a late symptom in PD.  If the symptom is early, this would suggest it’s not PD.

(10:36) PD diagnostic criteria – UK PD Society Brain Bank Criteria (Hughes et al, JNNP; 55: 181-184)
(See the slide)
Must have bradykinesia (slowness of movement)
Must have one or more of rigidity, tremor at rest, or postural instability but not at onset

In PD, postural instability usually begins 5-7 years in.

Patients with PD almost always survive ten years and often many more years than that.

(13:30) Atypical parkinsonian disorders
* Often confused with PD, AD, and other dementias
* Clinical diagnostic criteria for PD, AD, and the atypical parkinsonian disorders have imperfect sensitivity and specificity
* Diagnosis is made clinically as all diagnostic studies only support clinical suspicion
* ONLY WITH FOLLOW-UP can many “red flag” features be identified to improve diagnostic accuracy.  Ask about these at each visit.

(15:15) PD vs. atypical parkinsonian disorders (from Quinn, JNNP suppl: 78-89)

Clues for PD: asymmetric onset of movement dysfunction; significant and sustained benefits to dopaminergic medications (though tremor may not respond); classic resting tremor (or unilateral pill-rolling tremor)

Note: those with MSA may have a low-amplitude somewhat jerky postural tremor of the fingers or hand.

Clues for atypical parkinsonian disorders (PSP, CBS, MSA, DLB): fairly symmetric onset of movement dysfunction (except CBS which is highly asymmetric); poor, transient or no benefit to dopaminergic medications

Red flags to atypical parkinsonian disorders: few are absolute; may not be present at presentation so re-evaluate for these at every visit

(17:20) ALERT for Atypical Parkinsonian Disorders

ALERT is a helpful acronym for approaching these syndromes.

A= atypical for Parkinson disease
* apraxia and/or myoclonus (CBS or AD with parkinsonism)
* saccade changes (slow saccades or vertical ophthalmoplegia is PSP, delayed/apraxic in CBS, and hypermetric in MSA)
* parietal/sensory dysfunction (extinction, cortical sensory loss, alien limb in CBS)
* cerebellar or upper/lower motor neuron signs (MSA)
* certain types of dystonia or dyskinesia:
– retrocollis, blepharospam/eyelid opening “apraxia” or trunk dystonia in PSP
– anterocollis or levodopa-induced facial/oral dyskinesias in MSA
– limb dystonia in CBS or MSA
* faster progression, including “wheelchair sign” (early use of wheelchair – within 3-5 years)

L= lack of response to medications (poor, transient or no benefit to an adequate trial of levodopa – 1000mg/day).  One small exception, if tremor-predominant PD, a trial of 1000mg/day may not be warranted.

E= early (compared to PD):
* falls/postural instability (PSP)
* dysphagia, dysarthria, bulbar dysfunction (PSP, MSA)
* dementia, executive dysfunction, impulsivity, apathy, personality change, or pseudobulbar affective lability (DLB, CBS, PSP)
* hallucinations/delusions (DLB)
* autonomic dysfunction such as constipation and orthostatic hypotension (MSA)

R= refer to resources (second opinion to movement disorder specialists, physical/occupational/speech and swallow therapy – ancillary services become mainstay of treatment; CurePSP)

T= treat symptomatically (even when unsure of the diagnosis)

(23:13) Autonomic dysfunction
(See slide for a list of symptoms/features)

Patients with orthostatic hypotension may not have lightheadedness but may have fatigue, confusion, visual blurring, and the “coat hanger sign.”

Those with erectile dysfunction rarely voice this to the physician.

These are problems that can often be treated and are disabling.

PROGRESSIVE SUPRANUCLEAR PALSY – symptoms, variants, imaging, pathology

(25:01) Progressive Supranuclear Palsy
(see slide)

Bradykinesia tends to be axial.  Difficulty getting up from a chair.  Or getting back into a chair.  Tremor is uncommon.

Rigidity is axial.  Rigidity is often at neck.

Supranuclear palsy – both up and down.  Key diagnostic feature.  Slow vertical saccades – this can be found before supranuclear palsy.  (26:00 – video and audio out of synch for several seconds.)  Frequent saccadic instrusions.

Retrocollis.

Prominent bulbar dysfunction early on.

Frontal dysfunction.  Prominent apathy.  Executive dysfunction.  Impulsivity.  Applause sign – shows perseveration (from frontal lobe dysfunction); not specific to PSP; rarely seen in PD.

(28:18) PSP Variants (from Williams & Lees, Lancet Neurology 2009.  from Dickson et al, Curr Opin Neurol 2010)

PSP-Richardson syndrome: classic presentation; accounts for only approx 25% of PSP pathology; originally described in 1964 by John Steele, who is still living, Richardson, and neuropathologist Olszewski

PSP-Parkinsonism: can have tremor and partial/temporary levodopa response (similarities to Parkinson disease); more benign course than PSP-RS; nearly as common as PSP-RS

PSP-CBS
PSP-Nonfluent Aphasia
PSP-Frontotemporal dementia
PSP-Pure Akinesia with Gait Freezing
Mixed pathologies

(29:50) Imaging features of PSP
(see slide)
Hummingbird/penguin sign in midbrain
Morning glory sign

(30:24) Pathological changes of PSP
(see slide)

CORTICOBASAL SYNDROME – symptoms, variants, imaging, pathology

(31:05) Corticobasal Syndrome
(see slide)

Corticobasal Degeneration now used for pathological confirmation.  During life, we call this corticobasal syndrome.  Only about 50% of those diagnosed with CBS during life are found to have CBD upon autopsy.  30% have Alzheimer’s pathology.  20% have Lewy body pathology.

Often presents unilaterally.

Important to see a saccade.

May present with early frontal dementia.

(33:21) CBS Variants (from Armstrong et al, Neurology 2013)
PSP Syndrome
Frontal-behavioral spatial syndrome
Nonfluent/agrammatic Primary Progressive Aphasia
Mixed Pathologies (with Parkinson Disease, with Dementia with Lewy bodies)

[Robin’s note: Isn’t “corticobasal syndrome” a variant??]

(34:00) Imaging features of CBS
(see slide)

(34:13) CBD Pathology
(see slide)

MULTIPLE SYSTEM ATROPHY – symptoms, imaging, pathology

(34:37) Multiple System Atrophy
(see slide)

MSA subtypes: MSA-P and MSA-C.  All patients have to have dysautonomia (orthostatic hypotension or a combo of urinary incontinence and, with men, erectile dysfunction).

(36:15) Red flags suggesting MSA
(see slide)

Anterocollis

Inspiratory stridor or expiratory sighs

Pseudobulbar affect

(38:00) Imaging features of MSA
(see slide)

Hot cross bun sign

(38:15) MSA Pathology
(see slide)

DEMENTIA WITH LEWY BODIES – symptoms

(38:51) Dementia with Lewy Bodies/Diffuse Lewy Body Disease
(see slide)

Symmetric parkinsonism (often no tremor) with early dementia

Pseudo-delirium

Sensitive to antipsychotic medication

Greater extent of Lewy bodies in brain (especially in cortex)

GENERAL

(40:32) Overlapping symptoms in neurodegenerative disorders
cognitive – emotional – sleep/wake cycle – autonomic – sensory – movement

(41:30) Non-motor symptoms
(see slide)

cognitive – emotional – sleep – fatigue – autonomic – sensory

These can be very disabling.

VIDEOS THAT ILLUSTRATE SYMPTOMS

(43:00) Shawn Smyth, MD presents some videos that illustrate symptoms, which are useful during evaluation and diagnosis.

Woman with anguished look with PSP.

(43:20) Evaluating saccades in woman with PSP.  Evaluating optokinetic nystagmus.

(44:24) Evaluating retropulsion in PSP.

(44:37) Evaluating rigidity in neck and arms in PSP.

(44:50) Evaluating bradykinesia of PSP (unusual).

(45:40) Applause sign in PSP.

(46:04) Clenched-fist dystonia with irregular postural tremor in CBS.

(46:24) Asymmetric bradykinesia and lefthand dystonia in CBS.

(46:36) Apraxia in CBS.

(47:10) Squeaky hypophonia and dysarthria in MSA.

(47:29) Cerebellar signs in MSA.

(48:10) Wide cadence and irregular gait in MSA.

ANCILLARY TESTING

(48:27) Stephen Reich, MD discusses ancillary testing
(see slide)

MRI is worthwhile unless the patient seems to be classic for PD

DaT scan cannot distinguish between any of the PD and atypical parkinsonian disorders

Not challenging: distinguishing between PD and essential tremor.

Routine lab tests: vitamin B12, thyroid

MEDICATION MANAGEMENT

(51:09) Medication management of these syndromes
* Levodopa: test 1000mg/day immediate release (optimally received on an empty stomach during the waking part of the day)
* Cholinesterase inhibitors (rivastigmine) in DLB
* Quetiapine or clozapine for hallucinations, delusions or agitation, used cautiously
* SSRIs or TCAs for depression or anxiety.  Beware of medication interactions with other antidepressant, antipsychotic, or dopaminergic.  Shy away from TCA if constipation or OH is present.
* Levetiracetam or clonazepam for myoclonus, especially in CBS
* Try non-pharmacologic approaches to orthostatic hypotension first.  Review meds that might contribute to low BP.  Adequate salt intake.  Avoid hot baths/showers.  Lots of water.  Fludrocortisone, midodrine, droxidopa, or pyridostigmine for orthostatic hypotension.  Stockings, head of bed elevation, and abdominal binders can be considered.
* Botox injections for sialorrhea, dystonia, and blepharospasm/apraxia of eyelid opening

The atypical parkinsonian syndromes are NOT untreatable.  Medication does play a small role.

SUPPORTIVE MEASURES

(53:40) Supportive Measures
PT, OT, speech/swallow therapy
Social work/case management consultation
Support groups for patients/families, in-person or online
Palliative care

PSP MANAGEMENT

(54:18) Management of PSP
(see slide)

Trial of levodopa up to 3 months.  Taper or discontinue if unsuccessful or not tolerated.

Weak evidence for amitriptyline and amantadine.

He prefers UStep walker.

CBS MANAGEMENT

(55:22) Management of CBS
(see slide)

Try levodopa if significant bradykinesia.

Consider cholinesterase inhibitors for cognitive impairment

MSA MANAGEMENT

(55:50) Management of MSA
(see slide)

If MSA-P, judicious trial of levodopa.  Watch that orthostatic hypotension isn’t worsened.

See a urologist.

Not many therapies for MSA-C.

DLB MANAGEMENT

(56:42) Management of DLB
(see slide)

Not very responsive to levodopa but worth a trial.  Watch that mental status isn’t worsened and hallucinations aren’t caused.

Cholinesterase inhibitors can be helpful.  Worth trying them plus memantine.

Avoid antipsychotics unless necessary.

PROGNOSIS

(57:32) Prognosis for atypical parkinsonian syndromes

* Quite different from PD, where there’s a normal lifespan.  Cause of death is often unrelated to PD.
* Highly variable
* Most common causes of death due to disease itself — complications of immobility (DVT, infections with spesis), dysphagia (aspiration pneumonia), or injury from falls
* Generally have a lifepsan of <10 years from onset of symptoms, with variability.  Usually 6-10 years.

CONCLUSIONS

(58:15) Conclusions

* Atypical parkinsonian disorders have protean manifestations and can be challenging to diagnose at the front end

* ALERT acronym:
A= atypical for Parkinson disease
L= lack of response to medications
E= early falls, cognitive impairment, personality change, autonomic dysfunction (pay close attention to non-motor symptoms)
R= refer to resources (movement disorder specialists, CurePSP)
T= treat symptoms (even if you don’t have a diagnosis yet)

* It is important to consider these disorders in all middle aged or older patients, as early detection can improve quality of life for the patient and their caregiver/family

* Supportive care and a variety of symptomatic therapies can be offered.  Pay particular attention to the caregiver throughout the disease.

RESOURCES

(58:48) Resources

CurePSP, curepsp.org
AFTD, theaftd.org
ClinicalTrials.gov

[Robin adds: Brain Support Network, brainsupportnetwork.org – educational materials on PSP, CBS/CBD, MSA, DLB]