Week 7- Basal Ganglia Disorders (Additional Disorders) Flashcards
PART 1: INTRO AND SECONDARY PARKINSONISM
PART 1: INTRO AND SECONDARY PARKINSONISM
How is secondary parkinsonism different from PD?
Group of disorders that have features similar to PD but have a different etiology (one that is identified) while PD is idiopathic.
List some causes that can lead to secondary parkinsonism.
- Vascular
- Metabolic
- Toxic/Drug induced
- Infectious
- Tumor/mass
What are atypical parkinsonisms?
Group of neurodegenerative disorders other than PD that have some similar features to PD but have some different clinical features and underlying pathophysiology.
List some atypical parkinsonisms.
- Progressive supranuclear palsy
- Multiple systems atrophy
- Lewy body dementia
- Corticobasal degeneration
There are a ton of secondary parkinsonisms that look very similar to PD, but what one is so different from the others?
Vascular Parkinsonism
What are the 2 clinical features of vascular parkinsonism (caused by small CVAs)?
- Acute or delayed progressive onset of parkinsonism = 1 year after stroke with evidence of infarcts in or near BG.
- Insidious onset, extensive subcortical white matter lesions, + parkinsonism features.
What are the common symptoms of vascular parkinsonism?
Symmetrical lower-body parkinsonism
- gait unsteadiness (+ freezing, festinating)
- bradykinesia, akinesia, hypokinesia
- absence of tremors
- rigidity
- pyramidal signs
With vascular parkinsonism, we only see _____ involvement.
LE
- What is the treatment for vascular parkinsonism?
- Do they respond to levodopa?
- CVA management
- Not as well because they don’t have a direct depletion of dopamine.
PART 2: PROGRESSIVE SUPRANUCLEAR PALSY
PART 2: PROGRESSIVE SUPRANUCLEAR PALSY
What are the 4 most common atypical parkinsonisms?
- Progressive Supranuclear Palsy
- Multiple System Atrophy
- Lewy Body Dementia
- Cortical Basal Degeneration
- What is the most common atypical parkinsonism?
- What is the average age of onset?
- Progressive Supranuclear Palsy (PSP)
- 60s
- What is the pathophysiology of PSP?
- Accompanied by rapid ___________ and ________ loss.
- What is the hallmark of the disease?
- Where do we see the most involvement?
- Exact cause is unknown.
- astrogliosis (abnormal increase in astrocytes) and neuronal loss
- Accumulation of abnormal protein called tau.
- frontal lobe, BG, and brainstem
PSP Diagnosis:
- Typically diagnosed in mid ____.
- Early on, clinical __________ serves as primary diagnosis .
- On the MRI, we can see what 2 signs?
- What are some easy misdiagnosis?
- 60s
- examination
- “Morning Glory Sign” and “Hummingbird Sign”
- depression, dementia, Parkinsonisms
What are the SxS of PSP?
- Gait disturbances
- Loss of righting reaction
- Motor impulsivity (“Rocket Sign”)
- Severe axial rigidity
- Supranuclear opthalmoplegia
- Dysphagia and dysarthria (Spastic, hypernasal, hypokinetic, and monotonous)
- Frontal cognitive dysfunction
- Pseudobulbar affect
- Sleep disturbances
- “Surprised expression”
What 2 key feature are used to distinguish PSP from PD?
- gait instability
- early falls
With PSP, they fall ________ suddenly.
backwards
What is “Rocket Sign”?
Suddenly jump to feet from sitting position even without assistance, followed by falling back into chair. Failure of motor planning.
PSP is often seen with _______ rigidity, leading to constant leaning back position.
extensor
Supranuclear Opthalmoplegia:
- Limited _______ eye movement.
- Loss of __________.
- Impaired visual _________.
- Loss of visual _________.
- Loss of ________ control.
- VERTICAL (first definitive clue of PSP diagnosis)
- convergence
- saccades
- acuity
- eyelid
PSP Treatment:
- Is there an effective treatment for PSP?
- Anti-___ medications may be slightly effective, but tends to be minimal and short lasting (40% response rate).
- Amantadine, Botulinum injections, Anti-depressants sometimes used.
- No
- Anti-PD
PSP Prognosis:
- ________ progressive disease.
- Severe disability in __-__ years of onset; mortality commonly seen __-__ years.
- Serious complications include _________ and _____ w/ injury.
- rapidly
- 3-5 years; 5-8 years
- pneumonia and falls w/ injury
PART 3: MULTIPLE SYSTEMS ATROPHY
PART 3: MULTIPLE SYSTEMS ATROPHY
- Multiple Systems Atrophy (MSA) is a rare neurodegenerative disorder with + __________ dysfunction.
- There are _______-______ cases in the US.
- What are the 2 subtypes of MSA?
- What is the average age of onset?
- autonomic dysfunction
- 15000-50000
- MSA-P (parkinsonism) and MSA-C (cerebellar)
- 50s (rarely past 70)
MSA Pathophysiology:
- What is the cause?
- Most involvement in increase number of __________ as compared to astrocytes in PSP.
- What regions are most involved is MSA?
- unknown
- oligodendrocytes
- BG, cerebellum, pons, inferior olivary nucleus, intermediolateral column of thoracic and sacral spinal cord.
MSA Diagnosis:
- Clinical __________ serves as primary diagnosis.
- On the MRI, we can see what 2 signs?
- It is often misdiagnosed with what? How is this misdiagnosis often corrected?
- examination
- more widespread damage and “Hot Cross Bun” sign
- PD, corrected once patients do not respond to dopamine therapy.
What are the SxS of MSA?
- Autonomic symptoms
- Bradykinesia, rigidity, tremors
- Gait and limb ataxia
- Head/oral dyskinesias and dystonias
- Antecollis
- Pisa Syndrome
- Oculomotor disturbances
- Speech deficits
- Sleep disorders
- Most individuals with MSA will go through a ________ phase where their symptoms are entirely non-motor in nature and can go on for years before motor symptoms show up.
- Typically, the non-motor symptoms seen in the premotor phase are exclusively ________ in nature.
- premotor
- autonomic (Sexual dysfunction, urinary urge incontinence, orthostatic hypotension, inspiratory stridor, REM sleep behavior)
Autonomic Symptoms:
- What are some common things seen with autonomic symptoms of MSA?
- _________ is often first symptoms in males.
- BP irregularities, urinary/sexual dysfunction, respiratory/breathing problems, sleeping
- impotence
Bradykinesia, Rigidity, Tremors:
- More __________ appearance early on than PD.
- Tremors are of ________ frequency, _______ amplitude, can have jerky, stimulus-sensitive, myoclonic component.
- symmetric
- higher frequency, lower amplitude
Head/oral Dyskinesias and Dystonias:
- Orofacial dystonia is often a tipoff for MSA-__.
- What is “Coat-Hanger Pain”?
- MSA-P
- Pain in neck/shoulders when standing up
What is antecollis?
Dystonia of the neck resulting in excessive forward flexion, often associated with dysphagia.
- What is Pisa Syndrome?
- Results in significant ________ instability and frequent early falls.
- Lateral bending of the trunk with a tendency to lean to one side.
- postural
With oculomotor disturbances MSA-__ > MSA-__.
MSA-C > MSA-P
Speech deficits are often _____ but become unintelligible in later stages of MSA.
mild
What are some sleep disorders seen with MSA?
- OSA
- stridor
- REM sleep behavior disorder (acting out dreams)
Cognitive deficits are ____ with MSA until the very end of the disease progression.
RARE
MSA Treatment:
- Is there an effective treatment for MSA?
- Anti-PD medications only effective in about 1/3 patients, but are used with caution. Why?
- Medications are mainly for _________ management.
- Surgical intervention to prolong life in the form of tracheostomy, gastostromy often included in later stages of disease.
- No
- Because they can lead to worsening of OH, and the response usually lasts for <2-3 years.
- symptom management
MSA Prognosis:
- 50% of patients require walking aids within __ years after onset of motor symptoms.
- 60% become wheelchair-dependent after __ years.
- Average time to becoming dependent/bedridden is __-__ years.
- Mortality ranges from __-__ years after onset of symptoms.
- 3 years
- 5 years
- 6-8 years
- 5-10 years
Cerebellar phenotype and later onset of autonomic symptoms predict ________ disease progression.
slower
PART 4: LEWY BODY DEMENTIA AND CORTICOBASAL DEGENERATION
PART 4: LEWY BODY DEMENTIA AND CORTICOBASAL DEGENERATION
Lewy Body Dementia (LBD):
- Presence of dementia, prominent ____________ and __________, fluctuations in alertness, and gait & balance disorder.
- _______ most common type of progressive dementia (30% of all dementia cases).
- > _________ cases in US
- What is the average age of onset?
- Does it affect women or men greater?
- hallucinations and delusions
- 3rd most common
- 1 million-
- 75 years
- Men>women (4:1)
- What is the pathology of Lewy Body Dementia?
- Abnormal protein deposits (______ ________) develop in nerve cells.
- unknown
- lewy bodies
What are some risk factors for LBD?
- > 60 years old
- male>female
- certain comorbidities (PD, REM sleep behavior disorder)
- family history of LBD or PD
- Typically diagnosed through clinical examination.
- What is the only definitive way to confirm presence of LBD?
-Post-mortem autopsy
Can you have both LBD and PD?
Yes
What are the SxS of LBD?
- Cognitive decline EARLY
- Behavioral and personality change
- Parkinson’s-like movement disorders
- Autonomic dysfunction
- Loss of smell
- Sleep difficulties
Cognitive Decline:
- Appears _____ in LBD.
- Attention and executive function via ________ lobe and visuospatial via ________ lobe.
- Memory ______ early stages.
- Fluctuations between confusion and coherence.
- Hallucinations (___%), paranoid ideation.
- early
- frontal, parietal
- okay
- Hallucinations (80%)
What behavioral and personality changes are seen LBD?
- depression
- apathy
- anxiety
- agitation
What are some Parkinson’s-like movement disorders seen with LBD?
- slowed movement, rigidity, tremor, shuffled gait, falls
- stooped posture, balance problems
- dysphagia, hypophonia
Autonomic dysfunctions (although not as involved as MSA) is seen with LBD, what 3 things are most commonly seen?
- BP (hypotension)
- HR (bradycardia)
- GI (digestive dysregulation)
Sleep disorders are really common in those with LBD, what are some examples seen?
- REM sleep behavior disorder
- Insomnia
- Excessive daytime sleepliness
- Restless leg syndrome
What is often the first symptom of LBD?
REM sleep behavior disorder
LBD Treatment:
- Is there an effective treatment for LBD?
- Treatment is largely aimed at _______ management.
- What are some drugs used to manage symptoms of LBD?
- No
- symptom
- Cholinesterase inhibitors, Antipsychotics, Antidepressants, Clonazepam
LBD Prognosis:
-Mortality __-__ years after onset of symptoms. (Some variability, can survive up to 20 years!)
5-8 years
- LBD is often mixed up with _________ disease.
- What is the effect of this along with antipsychotic drugs?
- Alzheimer’s
- Antipsychotics used for Alzheimer’s can affect LBD patients more so and have more severe side effects.
Corticobasal Degeneration (CBD):
- _________ of atypical parkinsonisms
- Characterized by asymmetric parkinsonism symptoms + early _________ deficits.
- What is the age of onset?
- Does it affect men or women more?
- rarest
- cognitive
- 60-80 years
- women>men
- What is the pathophysiology of Corticobasal Degeneration?
- Focal _______ and _________ _____ neuronal loss.
- Glial lesions most commonly involving __________. Neurons give ________ appearance. Gives appearance of over-pronounced sulci (“brain shrinkage”).
- unknown
- cortical and substantia nigra
- astrocytes, ballooned
What are the SxS of CBD?
- parkinsonism symptoms
- cognitive impairments (tend to be present earlier than PSP)
- visuospatial impairments
- apraxia
- myoclonus
- dysphagia
- progressive aphasia
- apraxic speech
- CBD looks a lot like _____.
- What is a slight difference seen?
- PSP
- cognitive impairments come on quicker in CBD. Dementia, Alzheimer’s, and Frontal Behavioral-Spatial Syndrome can be seen in conjuction.
CBD Treatment:
- Is there an effective treatment for CBD?
- Treatment is largely supportive and ______-dependent.
- No
- symptom-dependent
CBD Prognosis:
-Mean survival of __-__ years from symptom onset. However, multiple cases with survival of >10 years have been reported.
-6-8 years
PART 5: DYSTONIAS AND TARDIVE DYSKINESIA
PART 5: DYSTONIAS AND TADIVE DYSKINESIA
- What is Dystonia?
- What are the 2 typical onsets of Dystonia?
- What are the 5 classifications of Dystonia?
- Hyperkinetic movement disorder characterized by involuntary muscle contractions that cause slow, repetitive movements or abnormal postures.
- childhood (early-onset) and adulthood (adult-onset)
- Focal, Segmental, Multifocal, Generalized, Hemidystonia
- Early-onset dystonia typically begins with _____ involvement.
- Adult-onset dystonia typically begins with _____ and/or _______ involvement.
- limb
- face and/or neck
Describe the 5 classifications of dystonia.
- Focal = 1 body region affected.
- Segmental = 2 or more continuous regions affected.
- Multifocal = 2 or more non-continuous regions.
- Generalized = Axial and 2 other areas in extremity.
- Hemidystonia = Half of body involved.
- What is the pathophysiology of dystonia?
- Imaging is normal, thought to be disruption of _____.
- Typically idiopathic, some cases genetic or acquired.
- BG
Dystonia is typically ________, _________, may be tremulous.
patterned, twisting
What are the common initial symptoms of dystonia?
- Sporadic foot cramping and/or toe dragging or excessive foot inversion during swing phase of gait.
- Severe hand cramping with writing.
Dystonia General Symptoms:
- Can see _______ dystonias causing excessive and rapid blinking or inability to open eyes entirely.
- Neck and trunk can be impaired, leading to significant __________ abnormalities.
- Limb involvement frequently leads to severe ____________.
- eyelid
- postural
- contractures
Characteristics of Dystonic Movements:
- Often will be intermittent in ______ stages, only appearing during voluntary movements or stress. Tends to be constant in ______ stages.
- Throughout all stages is shown to _________ with activity and ___________ with rest.
- Can be circumstantial, what does this mean?
- early, late
- worsened with activity and improves with rest
- May only affect one specification of movement, while allowing others to occur unimpeded. (Ex. musician with dystonia when trying to use her hand to play instrument, but can write easily)
What is convergence disorder?
-Neurological impairments with psychiatric undertone. Dystonia may be a subtype of it because it’s not seen on imaging.
What are the 2 treatment methods for dystonia?
- Pharmacological
- Surgical
- Focal dystonia responds well to _________ toxin.
- What are some other pharmacological drugs used?
- botulinum (botox)
- Anticholinergic agents, GABAergic agents, and dopaminergic agents have shown to have some effect on managing symptoms for more involved classifications of dystonia, though mixed results.
What are some surgical interventions used to treat dystonia?
- Deep Brain Stimulation (DBS)
- Thalamotomy, pallidotomy, anterior cervical rhizotomy may be performed.
When is deep brain stimulation (DBS) used to treat dystonia?
When medications have failed, or side effects are too severe.
Dystonia Prognosis:
- Dystonia is considered to be a ________ disease, though HIGH variability in what that looks like person to person.
- ____________ onset more likely to spread to other body regions.
- progressive
- childhood onset
What is Tardive Dyskinesia?
Drug-induced disorder characterized by involuntary and uncontrolled stiff, jerky movements of face and body.
What are the common drugs that cause Tardive Dyskinesia?
- Amphetamine, methamphetamine, haloperidol (recreational)
- Phenothiazines (neuroleptic for schizophrenia) (prescribed)
- How many cases of Tardive Dyskinesia are there in the US?
- What are the risk factors?
- ~500,000 cases in US
- Risk factors: Age (>55 years), older women, amount of drug ingested, long-term use of drug, alcohol or drug abuse, black and Asian populations.
How is Tardive Dyskinesia diagnosed?
- review of medication Hx
- clinical examination
Tardive Dyskinesia Symptoms:
- _____, ___________ onset of symptoms after ingestion of medication.
- Dyskinesias of ______ most common (grimacing, sticking out tongue, sucking or fish-like facial movements common).
- Choreoathetoid or dystonic movements in limbs.
- Abnormal postural tone, abnormal postural adjustments (↑ extension of trunk, lordosis, neck flexion and rotation).
-slow, gradual
-face
-
Tardive Dyskinesia Treatment:
- __________ or dosage adjustment of causative medication.
- Currently 2 PDA-approved medications (Deutetrabenazine and Valbenazine).
cessation
Tardive Dyskinesia Prognosis:
- Highly variable.
- Typically see an __________ course, with long-term presence of symptoms.
- Some patients can see symptoms reversed with ___________ of medication,
- irreversible
- cessation
PART 6: HUNTINGTONS DISEASE
PART 6: HUNTINGTONS DISEASE
What is Huntington’s Disease (HD)?
Genetic, progressive, neurodegenerative disease characterized by uncontrolled movements, cognitive dysfunction and behavioral changes due to a HYPERACTIVITY of basal nuclei circuitry.
- Huntington’s Disease is considered to be _____ with only 30000 US cases.
- What is the age of onset?
- Is it more common in caucasian or asian/african?
- rare
- 30-50s (juvenile onset (<20) and late onset (>59) less common)
- caucasian
HD Pathophysiology:
- What is the cause?
- Normal genes produce protein called huntingtin, in HD that protein is cut into smaller, toxic fragments which accumulate in neurons. What does this lead to?
- Early stages of HD characterized by loss of projection neurons of the striatum in the _________ pathway, causing disinhibition of thalamus.
- Loss of striatal projection neurons in ________ pathway, as well as cortical neurons, become involved in later stages of disease.
- chromosomal abnormality (DOMINANT autosomal trait)
- Leads to disruption of normal neuronal function, atrophy, neuronal death; also leads to severe loss of neurons in caudate and putamen.
- indirect (NO-GO)
- direct (GO)
How is HD diagnosed?
- Review of family history
- Genetic testing
- Clinical examination
- Radiographic evidence
What are the SxS of HD?
- Movement, cognitive and psychological disorder
- Choreiform movements
- Motor impersistance
- Dystonia
- Ataxia
- EOM and visuospatial impairments
- Speech and swallowing deficits
- Impaired memory, attention, executive function
- Mood changes, depression, anxiety, uncharacteristic anger & irritability
- As disease progresses, athetosis, akinesia, & bradykinesia develop
What are choreiform movements?
- Involuntary, rapid, irregular and jerky movements.
- Extremities, trunk, face.
- What is motor impersistence?
- What is “Fly-catcher’s tongue”?
- Inability to maintain a voluntary muscular effort.
- Patients have hard time sustaining tongue within jawline.
- _________ is seen in later stages of HD.
- ____ is very common.
- Dementia
- OCD
What are the HD SxS progression 4 main stages?
- Pre-Manifest
- Early Stage
- Middle Stage
- Late stage
What is the prodromal phase?
Confirmation through + genetic test without SxS.
WHat are the 3 SxS categories of HD?
- Motor
- Cognitive
- Psychiatric
Pre-Manifest:
Motor
-_____ gait changes
Cognitive
-difficulty with complex _________ tasks
Psychiatric
-___________, irritability, aggression
Motor -mild gait changes Cognitive -difficulty with complex thinking tasks Psychiatric -depression, irritability, aggression
Early Stage:
Motor
-mild ________, ________ RAMs, mild ________ in tone, _____ dysfunction.
Cognitive
-mild problems with ________, __________, organizing, and prioritizing tasks.
Psychiatric
-__________, depression, irritability
Motor
-Mild chorea, decreased RAMs, mild increases in tone, EOM dysfunction.
Cognitive
-Mild problems with planning, sequencing, organizing, prioritizing tasks.
Psychiatric
-sadness, depression, irritability
Middle Stage:
Motor
-_________, motor impersistance, dystonia, rigidity and spasticity, voluntary movement abnormalities, incoordination, _________ deficits/falls, dysphagia, dysarthria.
Cognitive
-Intellectual decline, _______ loss, perceptual problems, lack of insight or self-awareness, breakdown with _____-______.
Psychiatric
-Apathy, perseveration, ___________, antisocial and suicidal behavior, paranoia, delusions or hallucinations.
Motor
-Chorea, motor impersistance, dystonia, rigidity and spasticity, voluntary movement abnormalities, incoordination, balance deficits/falls, dysphagia, dysarthria.
Cognitive
-Intellectual decline, memory loss, perceptual problems, lack of insight or self-awareness, breakdown with dual-task.
Psychiatric
-Apathy, perseveration, impulsivity, antisocial and suicidal behavior, paranoia, delusions or hallucinations.
Late Stage:
Motor
-___________, rigidity and spasticity, severe voluntary movement abnormalities, dysarthria, dysphagia, incontinence.
Cognitive
-Global, ________ dementia.
Psychiatric
-__________
Motor
-Bradykinesia, rigidity and spasticity, severe voluntary movement abnormalities, dysarthria, dysphagia, incontinence.
Cognitive
-Global, ________ dementia.
Psychiatric
-__________
HD Treatment:
- Is there effective treatment for HD?
- Largely __________ management.
- Generally pharmaceutical interventions are not started until _________ interferes with function.
- No
- symptom
- chorea
HD Prognosis:
- Mortality: __-__ years after onset
- Cause often __________ failure
- _______ common
15-25 years
- respiratory
- suicide
What is a HD outcome measured used?
Unified Huntington’s Disease Rating Scale (UHDRS)
