Nervous System & Special Senses

Parkinson disease: managing motor and nonmotor complications

Clinical Overview and When to Suspect Parkinson Disease

— Tremor at rest (4–6 Hz, "pill-rolling"), often asymmetric

— Rigidity (cogwheel or lead-pipe)

— Akinesia/bradykinesia (required for diagnosis)

— Postural instability (later feature; early falls suggest atypical parkinsonism)

— Unilateral resting tremor that improves with action

— Micrographia, hypophonia, masked facies, decreased arm swing, shuffling gait

— Subtle nonmotor prodrome: REM sleep behavior disorder (RBD), hyposmia, constipation, depression, often preceding motor symptoms by 5–10 years

Board pearl: Asymmetry of motor signs is one of the most discriminating features favoring idiopathic PD over atypical parkinsonian syndromes (PSP, MSA, CBD), which tend to present more symmetrically and with early postural instability, vertical gaze palsy, dysautonomia, or apraxia.

Step 3 management: Once PD is suspected, the outpatient task is not to "rule in" with imaging but to (1) confirm levodopa responsiveness, (2) screen for nonmotor symptoms at every visit, (3) anticipate motor fluctuations and dyskinesias, and (4) coordinate physical therapy and caregiver support from the time of diagnosis.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta with α-synuclein–positive Lewy body inclusions.

Median age of onset is ~60 years; men affected ~1.5× more than women. Prevalence rises sharply after age 65.

Core motor features (TRAP):

Suspect PD in an older adult with:

Diagnosis is clinical, per MDS criteria: bradykinesia plus rest tremor or rigidity, with supportive features (clear levodopa response, olfactory loss, RBD) and absence of red flags (early falls, early autonomic failure, rapid progression, symmetric onset, cerebellar signs).

Step 3 framing prioritizes longitudinal ambulatory management of motor fluctuations, nonmotor symptoms (cognition, mood, autonomic, sleep), and transitions of care as disability accrues.

Presentation Patterns and Key History

— Unilateral tremor, subtle bradykinesia, handwriting changes, soft voice

— Patient often reports a spouse noticing reduced facial expression or arm swing

— Functional impact mild; ADLs preserved

— Bilateral symptoms, postural instability on pull test, wearing-off (return of symptoms before next dose), early peak-dose dyskinesias

— Nonmotor: constipation, orthostatic lightheadedness, urinary urgency, depression, anxiety, sleep fragmentation

— Falls, freezing of gait, dysphagia, severe dyskinesias, on-off fluctuations, hallucinations, cognitive impairment evolving to PD dementia (PDD) when dementia emerges >1 year after motor onset

— Medication diary: timing of doses vs. "on/off" periods

— Falls in last 3 months, freezing episodes, near-misses

— Sleep: vivid dreams, dream enactment (RBD), excessive daytime sleepiness, sleep attacks on dopamine agonists

— Mood (PHQ-9), anxiety, apathy, hallucinations (often visual, well-formed, initially with insight)

— Autonomic: orthostatic symptoms, constipation, urinary symptoms, sexual dysfunction, drooling

— Impulse control disorders (ICDs): gambling, hypersexuality, binge eating, compulsive shopping — directly ask, especially on dopamine agonists

Key distinction: PD with dementia (PDD) = motor symptoms ≥1 year before cognitive decline. Dementia with Lewy bodies (DLB) = cognitive decline first or within 1 year of motor symptoms, with prominent fluctuating cognition, early visual hallucinations, and severe neuroleptic sensitivity. Treatment overlaps but prognostic counseling differs.

Board pearl: Always ask about ICDs by name at every visit on a dopamine agonist; patients rarely volunteer them, and missed gambling losses are a classic Step 3 stem.

Early/de novo PD (Hoehn & Yahr 1–2):

Mid-stage PD (H&Y 2.5–3):

Advanced PD (H&Y 4–5):

Targeted history at every visit:

Medication review for drug-induced parkinsonism: metoclopramide, prochlorperazine, typical antipsychotics, risperidone, even high-dose SSRIs occasionally.

Physical Exam Findings and Hemodynamic Assessment

— Resting tremor: observe hands at rest in lap; activate with mental task (serial 7s) to bring out subtle tremor. Disappears with action initially.

— Bradykinesia: finger taps, hand opening/closing, pronation-supination — look for decrement in amplitude and speed with repetition (the defining feature, not slowness alone).

— Rigidity: passive movement at wrist/elbow with contralateral activation (Froment maneuver). Cogwheeling = rigidity + tremor.

— Gait: decreased arm swing (often unilateral early), stooped posture, shuffling, en bloc turning (multiple small steps), festination, freezing at thresholds/doorways.

— Pull test: stand behind patient, warn them, sharp pull on shoulders — retropulsion >2 steps or fall = impaired postural reflexes.

— Vertical gaze palsy (PSP)

— Cerebellar ataxia or pyramidal signs (MSA)

— Cortical signs: apraxia, alien limb, cortical sensory loss (CBD)

— Early symmetric parkinsonism without tremor

— Check orthostatic vitals at every visit: supine after 5 min, then 1 and 3 min standing

— Neurogenic orthostatic hypotension (nOH): SBP drop ≥20 mmHg or DBP ≥10 mmHg without compensatory HR rise >15 bpm — points to autonomic failure (common in PD, defining in MSA)

— Supine hypertension frequently coexists — measure supine BP before prescribing pressors

Step 3 management: Document orthostatics and a MoCA at baseline and annually; both drive medication choices (avoid anticholinergics if MoCA low; cautious dopamine agonist use if orthostatic).

Board pearl: Decrement (fatigue and amplitude loss) on repetitive finger tapping is more specific for PD bradykinesia than simple slowness, which can reflect depression, hypothyroidism, or essential tremor coexisting with aging.

Motor exam:

Facial/bulbar: hypomimia, decreased blink rate, hypophonia, palilalia, drooling.

Red flags suggesting atypical parkinsonism — examine for:

Hemodynamic assessment (critical in PD):

Cognitive screen: MoCA preferred over MMSE (more sensitive to executive/visuospatial deficits typical of PD).

Diagnostic Workup — Initial Labs, Imaging, and Biomarkers

— TSH (hypothyroidism mimics bradykinesia)

— CBC, CMP, B12, folate (cognitive contributors)

— Ceruloplasmin and 24-hr urinary copper if onset <40 years → screen for Wilson disease; also slit-lamp for Kayser-Fleischer rings and LFTs

— Consider HIV, RPR if atypical course

— Indicated when atypical features or rapid progression present

— In idiopathic PD: typically normal

— Findings suggesting alternatives:

– "Hot cross bun" pons or putaminal atrophy → MSA

– Midbrain "hummingbird" sign → PSP

– Asymmetric cortical atrophy → CBD

– Extensive white matter disease → vascular parkinsonism

– Communicating hydrocephalus with gait apraxia + incontinence + cognitive decline → NPH

— Visualizes presynaptic dopamine transporter density in striatum

— Distinguishes neurodegenerative parkinsonism (PD, MSA, PSP, CBD = abnormal) from essential tremor, drug-induced parkinsonism, psychogenic, and vascular parkinsonism (normal)

— Does not distinguish PD from atypical parkinsonian syndromes

— Order when diagnosis is uncertain after clinical evaluation

— α-synuclein seed amplification assay (SAA) in CSF or skin shows high sensitivity/specificity for synucleinopathies; increasingly used in research and specialty practice

— Olfactory testing (UPSIT) supports diagnosis; hyposmia present in >90%

Key distinction: A levodopa challenge showing robust, sustained improvement (≥30% on UPDRS-III) is a supportive criterion for PD. Atypical parkinsonian syndromes typically show poor or transient response.

Board pearl: Don't order DaTscan to distinguish PD from MSA/PSP — it's abnormal in all. Order it when the question is "is this neurodegenerative parkinsonism at all, or essential tremor / drug-induced?"

PD is a clinical diagnosis. Routine labs and structural imaging are used to exclude mimics, not confirm PD.

Initial labs in a new parkinsonism workup:

Structural MRI brain:

DaTscan (¹²³I-ioflupane SPECT):

Emerging biomarkers:

Diagnostic Workup — Advanced and Confirmatory Studies

— Tilt-table testing, heart rate variability, Valsalva ratio, thermoregulatory sweat testing

— Severe early autonomic failure with parkinsonism → MSA-P

— Confirms REM sleep behavior disorder when history suggestive

— RBD without parkinsonism conveys ~80–90% lifetime risk of converting to a synucleinopathy (PD, DLB, MSA) over 10–15 years

— Indicated when cognitive complaints emerge, for differentiating PD-MCI, PDD, DLB, depression-related cognitive slowing, and to plan driving/work capacity

— Consider if onset <50, strong family history, or specific ethnic backgrounds

— Common variants: LRRK2 (Ashkenazi Jewish, North African Berber populations), GBA (faster cognitive decline), PARKIN/PINK1/DJ-1 (young-onset autosomal recessive), SNCA duplications/triplications (rare, severe)

— Genetic counseling required; results affect prognosis, clinical trial eligibility, and family planning

— Carbidopa-levodopa 250 mg with domperidone pretreatment (outside US) or escalating doses over weeks; ≥30% UPDRS-III improvement supports PD

— FDG-PET patterns can help differentiate PSP, MSA, CBD when DaTscan ambiguous

— MIBG cardiac scintigraphy: reduced uptake in PD/DLB (postganglionic sympathetic denervation); preserved in MSA — useful where available

Step 3 management: A patient with isolated RBD on polysomnography should be counseled about elevated risk of future synucleinopathy, given a safe sleep environment plan (remove bedside hazards, padded bedrails, partner safety), and treated with melatonin 3–12 mg first-line; clonazepam 0.25–1 mg is second-line but avoided in elderly with cognitive impairment or sleep apnea.

Board pearl: A young patient with parkinsonism, dystonia, psychiatric symptoms, and abnormal LFTs needs Wilson disease workup before anything else — missed diagnosis is testable and treatable.

Autonomic testing (when MSA suspected or severe dysautonomia):

Polysomnography:

Neuropsychological testing:

Genetic testing:

Levodopa challenge / acute dopaminergic test:

Functional imaging beyond DaTscan:

Risk Stratification and First-Line Management Logic

— How disabling are symptoms? Mild and non-disabling → may defer therapy or use MAO-B inhibitor; moderate/disabling or affecting livelihood → start dopaminergic therapy.

— Age and cognitive status: ≥65 or any cognitive concern → favor carbidopa-levodopa over dopamine agonists (lower risk of hallucinations, ICDs, somnolence).

— <65 with predominant tremor and intact cognition: dopamine agonist or MAO-B inhibitor reasonable initial choices, but levodopa is increasingly used first-line in all ages per current evidence (LEAP, PD-MED trials).

— Comorbid depression: consider that dopaminergic therapy may improve mood; pramipexole has antidepressant data.

— Levodopa is the most effective symptomatic agent; delaying it does not preserve neurons or prevent dyskinesia — dyskinesia correlates with disease duration and dose, not time on levodopa.

— Start at the lowest effective dose; titrate to symptom relief, not to "normalize" the exam.

— Aerobic exercise (≥150 min/week of moderate-intensity, including resistance training) has the strongest evidence for symptom benefit and possible neuroprotection.

— Referral to PT (LSVT BIG) and speech therapy (LSVT LOUD) for hypophonia.

— Nutrition, fall-prevention home assessment, driving evaluation if any concern.

— Connect with PD support organizations early.

Step 3 management: When a 70-year-old with bothersome bradykinesia presents at diagnosis, start carbidopa-levodopa 25/100 mg three times daily rather than a dopamine agonist; safer side-effect profile and better symptom control in older adults.

Board pearl: "Levodopa-sparing" strategies are largely obsolete — current guidance favors using the most effective agent that controls symptoms with the fewest side effects, which is usually levodopa.

Therapy is symptomatic, not disease-modifying. No agent proven to slow progression.

Decision framework at diagnosis:

Key trial-informed principles:

Nonpharmacologic foundation from day one:

Set expectations: PD is a chronic, progressive but treatable condition; many patients live 15–20+ years from diagnosis.

Pharmacotherapy — First-Line Drug Regimen

— Standard starting regimen: 25/100 mg TID, 30–60 min before meals (protein competes with absorption)

— Titrate by ½–1 tablet every few days as needed

— Most effective for bradykinesia and rigidity; tremor response variable

— Side effects: nausea (mitigated by carbidopa or taking with a small carb snack), orthostasis, somnolence, hallucinations, dyskinesias with chronic use

— Less efficacious than levodopa but lower early dyskinesia risk

— Avoid in age ≥70, cognitive impairment, hallucinations, prior ICD, severe daytime sleepiness

— Side effects to counsel about: ICDs, sleep attacks (do not drive if sedating), peripheral edema, orthostasis, hallucinations

— Renally cleared (pramipexole, ropinirole) → dose-adjust in CKD

— Modest symptomatic benefit; useful as monotherapy in mild disease or adjunct for wearing-off

— Mind serotonin syndrome risk with SSRIs/SNRIs/tramadol/meperidine (clinically rare but boards-favored)

— NMDA antagonist; mild parkinsonism benefit and specifically reduces levodopa-induced dyskinesia (extended-release form ADS-5102 FDA-approved for this)

— Avoid in renal failure, elderly with cognitive issues (confusion, livedo reticularis, ankle edema)

— Only for younger patients with tremor-predominant disease; avoid in elderly (Beers list) and any cognitive impairment

— Always given with levodopa; extend levodopa half-life to reduce wearing-off

— Tolcapone requires LFT monitoring (hepatotoxicity)

Step 3 management: When wearing-off appears, options include (1) shortening levodopa dose interval, (2) adding entacapone or opicapone, (3) adding a MAO-B inhibitor, or (4) switching to extended-release/inhaled levodopa. Choose based on dyskinesia profile and comorbidities.

Board pearl: Never abruptly stop levodopa or dopamine agonists — risk of neuroleptic malignant–like syndrome (parkinsonism-hyperpyrexia syndrome). Continue dopaminergics perioperatively, including the morning of surgery, via NG tube if needed.

Carbidopa-levodopa (immediate release):

Dopamine agonists (pramipexole, ropinirole, rotigotine patch):

MAO-B inhibitors (selegiline, rasagiline, safinamide):

Amantadine:

Anticholinergics (trihexyphenidyl, benztropine):

COMT inhibitors (entacapone, opicapone, tolcapone):

Advanced Therapies — Device-Aided and Surgical Management

— Targets: subthalamic nucleus (STN) — allows medication reduction; globus pallidus interna (GPi) — better for dyskinesias, may be safer cognitively

— Best candidates: <70 years (flexible), levodopa-responsive symptoms, no dementia, no untreated depression, no significant axial symptoms unresponsive to levodopa (DBS does not improve symptoms that don't respond to levodopa, except tremor)

— Benefits: smoother "on" time, ~50% medication reduction, reduced dyskinesia

— Risks: hemorrhage (1–2%), infection, hardware issues, mood/cognitive changes, dysarthria

— Unilateral; FDA-approved for tremor-predominant PD

— Incisionless alternative for patients who decline or cannot tolerate DBS

— Continuous infusion via PEG-J tube

— Reduces off-time; for patients unsuitable for DBS or who prefer pump

— Complications: tube/stoma issues, vitamin B6/B12 deficiency and peripheral neuropathy — monitor levels

— Intermittent rescue pen for unpredictable off-episodes; onset 10–20 min

— Continuous SC infusion (Onapgo) newly available for fluctuations

— Premedicate with antiemetic — not ondansetron (severe hypotension) — use trimethobenzamide

Step 3 management: Refer to a movement disorders specialist for DBS evaluation when off-time exceeds ~2 hours/day or dyskinesias are disabling despite optimal medical therapy. Pre-op workup includes neuropsychological testing, MRI, and levodopa challenge.

CCS pearl: In an inpatient PD patient who can't take PO (NPO, ileus), do not skip dopaminergics — convert to rotigotine transdermal patch (approximate 1:1 equivalence chart) or NG levodopa. Consult neurology promptly; abrupt withdrawal can precipitate fatal hyperpyrexia.

Indication for advanced therapy: motor fluctuations or dyskinesias refractory to optimized oral medications, with preserved levodopa responsiveness, without significant dementia or uncontrolled psychiatric illness.

Deep brain stimulation (DBS):

Focused ultrasound thalamotomy (MRgFUS):

Levodopa-carbidopa intestinal gel (LCIG, Duopa):

Subcutaneous apomorphine:

Inhaled levodopa (Inbrija): rescue for off-episodes, onset ~10 min.

Special Populations — Elderly and Renal/Hepatic Impairment

— Polypharmacy is the major driver of harm. Reconcile every visit.

— Avoid anticholinergics (trihexyphenidyl, benztropine) and amantadine in cognitive impairment — both cause confusion, hallucinations, urinary retention.

— Dopamine agonists carry higher risk of hallucinations, orthostasis, ICDs, and sleep attacks; prefer carbidopa-levodopa monotherapy.

— Start low, go slow: levodopa 25/100 BID, titrate weekly.

— Aggressively address orthostasis: liberalize salt/fluid, compression stockings, head-of-bed elevation, midodrine, droxidopa, fludrocortisone (watch for supine HTN and CHF).

— Fall prevention: home PT/OT, remove rugs, assistive devices, vitamin D, bone density screening — PD doubles hip fracture risk.

— Pramipexole, ropinirole, amantadine are renally cleared — dose-adjust or avoid in CKD stages 4–5

— Carbidopa-levodopa requires no renal dose adjustment but check for orthostasis

— Rasagiline, selegiline mostly hepatic — usually fine in CKD

— Tolcapone contraindicated in any liver disease (fulminant hepatitis risk); monitor LFTs every 2–4 weeks if used

— Rotigotine, ropinirole, rasagiline metabolized hepatically — use cautiously

— Levodopa generally safe; carbidopa minimally metabolized

— Continue PD meds the morning of surgery with sip of water

— Avoid antiemetics that block dopamine: metoclopramide, prochlorperazine, promethazine, droperidol, haloperidol → all worsen parkinsonism

— Safe antiemetics: ondansetron, trimethobenzamide

— Postoperative delirium common; use quetiapine or pimavanserin if antipsychotic needed — never haloperidol or risperidone

Board pearl: A hospitalized PD patient who develops hallucinations is far more likely to be experiencing dopaminergic toxicity, delirium from infection/metabolic cause, or new dementia than worsening primary disease — search for triggers before adding antipsychotics.

Step 3 management: Audit medication list against the Beers criteria at every elderly PD visit; deprescribe anticholinergics, sedatives, and dopamine-blocking antiemetics.

Elderly (≥75):

Renal impairment:

Hepatic impairment:

Perioperative management:

Special Populations — Young-Onset and Pregnancy

— ~10% of cases; more likely genetic (GBA, LRRK2, PARKIN, PINK1)

— Slower motor progression but earlier and more severe dyskinesias and motor fluctuations

— Lower risk of early dementia; higher risk of dystonia (especially morning foot dystonia)

— Psychosocial burden: career, parenting, insurance, long-term disability planning

— Strong candidates for DBS when fluctuations emerge

— Counsel about genetic testing implications for siblings and children

— Rare but increasing as YOPD recognition grows

— Pregnancy may worsen motor symptoms; postpartum exacerbations described

— Levodopa-carbidopa: preferred during pregnancy if treatment required; limited human data but no clear teratogenicity signal; widely used

— Amantadine: contraindicated in pregnancy — associated with cardiac and limb malformations

— Dopamine agonists: limited data; ropinirole and pramipexole generally avoided; if needed, use lowest effective dose

— MAO-B inhibitors: insufficient data, generally avoided

— Anticholinergics: avoid

— Breastfeeding: dopamine agonists suppress prolactin and lactation; levodopa enters breast milk minimally — case-by-case discussion

— Extraordinarily rare; consider Wilson disease, juvenile Huntington (Westphal variant), dopa-responsive dystonia (Segawa, GCH1 mutation), monogenic PD, drug-induced (metoclopramide, antipsychotics)

— Dopa-responsive dystonia: dramatic, sustained response to low-dose levodopa — never miss this diagnosis

Key distinction: A child or young adult with parkinsonism and dystonia that worsens through the day and improves with sleep, responding completely to low-dose levodopa, has dopa-responsive dystonia, not PD — lifelong levodopa with excellent prognosis.

Step 3 management: In a woman of reproductive age newly diagnosed with PD, discuss contraception before starting amantadine, and plan a preconception medication review well in advance of pregnancy.

Young-onset PD (YOPD, onset <50):

Pregnancy and PD:

Pediatric parkinsonism:

Patients of childbearing potential on amantadine require contraception counseling.

Complications and Adverse Outcomes

— Wearing-off: predictable return of symptoms before next dose; emerges in ~50% by 5 years

— On-off fluctuations: unpredictable, more advanced

— Peak-dose dyskinesias: choreiform movements at maximal plasma levodopa

— Biphasic dyskinesias: at onset and offset of dose

— Freezing of gait (FOG): sudden inability to initiate steps, especially at thresholds; partially levodopa-responsive

— Falls and fractures: leading cause of injury; hip fracture risk markedly elevated

— PD-MCI in ~25% at diagnosis; progresses to PDD in 50–80% over 10–20 years

— Hallucinations (usually visual, well-formed): triggered by dopaminergics, anticholinergics, amantadine, infection, sleep deprivation

— Psychosis: delusions (often paranoid jealousy or "phantom boarder")

— Depression (~40%), anxiety (~30%), apathy

— Impulse control disorders with dopamine agonists

— Dopamine dysregulation syndrome: compulsive overuse of dopaminergic medications

— Neurogenic orthostatic hypotension with supine hypertension

— Constipation (often years before motor symptoms)

— Urinary urgency, sexual dysfunction

— Sialorrhea — botulinum toxin to salivary glands, glycopyrrolate

— Excessive sweating, seborrhea

— Insomnia, RBD, restless legs, excessive daytime sleepiness, sleep attacks

— Dysphagia → aspiration pneumonia (leading cause of mortality)

— Hypophonia, dysarthria

— Triggered by abrupt dopaminergic withdrawal or dose reduction

— Hyperthermia, rigidity, altered mental status, autonomic instability, elevated CK

— Treatment: restart dopaminergics urgently, supportive ICU care

Board pearl: Aspiration pneumonia is the most common cause of death in advanced PD — formal swallow evaluation (FEES or video swallow) at first sign of coughing with meals, weight loss, or recurrent pneumonia.

Step 3 management: Treat PD psychosis by first reducing/eliminating in this order: anticholinergics → amantadine → MAO-B inhibitors → dopamine agonists → reduce levodopa to lowest tolerated. If antipsychotic needed: pimavanserin (FDA-approved for PD psychosis) or quetiapine; avoid all other antipsychotics.

Motor complications:

Cognitive and psychiatric:

Autonomic:

Sleep:

Bulbar:

Parkinsonism-hyperpyrexia syndrome:

When to Escalate Care — ICU, Consult, or Inpatient Triage

— Parkinsonism-hyperpyrexia syndrome: ICU, IV fluids, cooling, restart dopaminergics, bromocriptine or dantrolene if severe

— Aspiration pneumonia with respiratory distress or sepsis

— Severe orthostatic hypotension with syncope and injury

— Acute psychosis with safety concerns to self or others

— Suicidality (depression and impulsivity heightened in PD)

— Acute mental status change — always evaluate for UTI, pneumonia, electrolyte disturbance, dehydration, medication effects before attributing to disease progression

— Diagnostic uncertainty or red flags for atypical parkinsonism

— Motor fluctuations or dyskinesias not controlled by primary care–level adjustments

— Consideration for DBS, MRgFUS, or pump therapies

— New cognitive decline or psychosis

— Day 1 orders for admitted PD patient:

– Continue home PD meds on exact home schedule — not "TID/QID" with hospital med-pass times; specify clock times

– Diet: aspiration precautions, swallow evaluation if any concern; consider protein-redistribution diet (most protein at dinner) if wearing-off prominent

– Activity: PT/OT consults early; fall precautions, bed alarm

– Avoid dopamine-blocking antiemetics and antipsychotics — flag in MAR

– DVT prophylaxis, bowel regimen (constipation universal)

– Orthostatic vitals

— Day 2–3: medication reconciliation, social work for discharge planning, neurology consult if symptoms changed

— Movement disorders neurologist, PD nurse specialist, PT/OT, speech therapy, social work, palliative care for advanced disease, neuropsychology, psychiatry

CCS pearl: The single most common avoidable inpatient harm in PD is missed or delayed levodopa doses. On the CCS, write a medication order with specific clock times that match home regimen (e.g., "carbidopa-levodopa 25/100 mg PO at 0600, 1000, 1400, 1800, 2200") and include "do not substitute or hold without neurology approval."

Board pearl: New confusion in a stable PD patient — workup for infection (UTI most common) before adjusting PD meds or labeling as progression.

Hospitalize urgently:

Urgent neurology referral (outpatient or inpatient):

Inpatient management essentials (CCS framing):

Multidisciplinary team:

Key Differentials — Same-Category Causes (Atypical Parkinsonism)

— Early postural instability with backward falls, vertical supranuclear gaze palsy (down-gaze first), axial rigidity, frontal cognitive features, "surprised" facial expression, "Mickey Mouse" or growling speech

— MRI: midbrain atrophy, "hummingbird" sign

— Poor/no levodopa response

— MSA-P (parkinsonian): symmetric parkinsonism + severe early dysautonomia

— MSA-C (cerebellar): ataxia predominant

— Severe orthostatic hypotension, urinary incontinence, erectile dysfunction, stridor, RBD

— MRI: putaminal atrophy with hyperintense rim, pontine "hot cross bun," cerebellar atrophy

— Preserved cardiac MIBG uptake (vs reduced in PD)

— Levodopa response often partial and short-lived

— Markedly asymmetric rigidity and apraxia, alien limb phenomenon, cortical sensory loss, myoclonus, dystonia

— Cognitive: nonfluent aphasia, executive dysfunction

— Dementia preceding or within 1 year of parkinsonism

— Fluctuating cognition, recurrent visual hallucinations, RBD, severe neuroleptic sensitivity

— DaTscan abnormal; treat motor symptoms cautiously (worsens hallucinations); cholinesterase inhibitors helpful for cognition

— Lower-body parkinsonism (gait predominant, less tremor), stepwise progression, vascular risk factors, extensive white matter disease/lacunes on MRI

— DaTscan often normal

— Poor levodopa response

Key distinction: Early autonomic failure + parkinsonism = MSA. Early falls + vertical gaze palsy = PSP. Asymmetric apraxia + alien limb = CBD. Cognition first + hallucinations + fluctuations = DLB. Idiopathic PD has unilateral onset, robust levodopa response, and autonomic features develop later.

Board pearl: Severe sensitivity to even small doses of typical or atypical antipsychotics (worsening parkinsonism, rigidity, confusion) is a defining feature of DLB — testable on Step 3.

Progressive supranuclear palsy (PSP):

Multiple system atrophy (MSA):

Corticobasal degeneration (CBD):

Dementia with Lewy bodies (DLB):

Vascular parkinsonism:

Key Differentials — Other-Category Causes

— Action/postural tremor, bilateral and symmetric, typically affects hands and head ("yes-yes," "no-no")

— Family history common (autosomal dominant)

— Improves with alcohol; treated with propranolol or primidone

— No bradykinesia, no rigidity, normal gait, normal DaTscan

— Symmetric onset, often with orofacial dyskinesia or akathisia

— Culprits: typical antipsychotics, risperidone, olanzapine (less), metoclopramide, prochlorperazine, lithium, valproate

— Resolves over weeks-to-months after discontinuation

— DaTscan normal

— Triad: gait apraxia (magnetic, wide-based), urinary incontinence, dementia

— MRI: ventriculomegaly out of proportion to atrophy

— Large-volume LP improves gait → predictive of shunt response

— Age <40, parkinsonism + dystonia + psychiatric symptoms + hepatic dysfunction

— Low ceruloplasmin, high 24-hr urinary copper, Kayser-Fleischer rings

— Juvenile-onset with rigidity and bradykinesia rather than chorea; family history of HD

— Manganese (welders, parenteral nutrition), carbon monoxide poisoning, MPTP exposure

— Hypothyroidism, B12 deficiency can mimic bradykinesia

— Abrupt onset, inconsistency on exam, distractibility, atypical features

— DaTscan normal

— Slow movement and flat affect without true bradykinesia decrement; resolves with antidepressant treatment

Step 3 management: A 68-year-old on metoclopramide for diabetic gastroparesis develops symmetric parkinsonism — stop the metoclopramide and reassess in 3–6 months before initiating dopaminergic therapy or considering PD diagnosis.

Board pearl: NPH gait is described as "feet stuck to the floor" / magnetic, distinguishing it from the festinating, shuffling gait of PD; both can coexist in older patients, so reassessment after each intervention matters.

Essential tremor (ET):

Drug-induced parkinsonism:

Normal pressure hydrocephalus (NPH):

Wilson disease:

Huntington disease (Westphal variant):

Toxin/metabolic:

Psychogenic (functional) parkinsonism:

Depression with psychomotor slowing:

Secondary Prevention, Discharge Planning, and Long-Term Strategy

— Aerobic exercise ≥150 min/week plus resistance training and balance work; tai chi, boxing programs, treadmill training all evidence-supported

— Mediterranean or MIND diet; adequate fiber and hydration for constipation

— Sleep hygiene; treat OSA if present

— Limit alcohol; smoking cessation (though smoking is paradoxically inversely associated with PD risk, it worsens overall outcomes)

— Annual influenza, COVID-19 boosters, pneumococcal (PCV20 or PCV15+PPSV23), RSV per current ACIP, Tdap, shingles — high stakes given aspiration pneumonia risk

— DEXA at baseline and per guidelines; vitamin D 800–1000 IU/day, calcium adequacy

— Bisphosphonate or denosumab per FRAX/T-score

— Carbidopa-levodopa with specific clock times (give the patient a printed schedule)

— Avoid newly prescribed metoclopramide, prochlorperazine, promethazine, haloperidol, risperidone — document on allergy/intolerance list

— Bowel regimen (polyethylene glycol daily standard)

— Orthostasis plan: compression, fluid/salt, midodrine PRN

— Antiplatelet/anticoagulation as indicated, recognizing fall risk vs benefit

— Begin discussions early while cognition intact: goals of care, healthcare proxy, code status, feeding tube preferences, DBS device decisions, driving

— Palliative care referral when advanced disease, recurrent hospitalizations, or significant caregiver burden

Step 3 management: At every PD follow-up, perform a structured review: (1) motor symptoms and fluctuations, (2) nonmotor symptom checklist, (3) medication adherence and side effects (ICD screen!), (4) falls, (5) cognition/mood, (6) caregiver well-being.

Board pearl: Caregiver burnout drives nursing home placement more than disease severity itself — assess and support caregivers as part of every PD encounter.

PD has no proven disease-modifying therapy, so "secondary prevention" focuses on preventing complications and maintaining function.

Lifestyle pillars (lifelong):

Vaccinations:

Bone health:

Cardiovascular and metabolic comorbidities: standard management with attention to orthostasis — avoid aggressive BP targets if neurogenic OH; choose non-CNS-depressing agents.

Discharge medication list essentials after PD-related admission:

Advance care planning:

Follow-Up, Monitoring Parameters, and Rehab/Counseling

— Newly diagnosed/stable: every 3–6 months

— Motor fluctuations, recent medication change, advanced disease: every 1–3 months

— Annual comprehensive review with neurologist

— MDS-UPDRS (or abbreviated motor exam) to track progression

— Hoehn & Yahr stage

— Orthostatic vital signs

— MoCA annually, more frequently if cognitive complaints

— PHQ-9 for depression, GAD-7 for anxiety

— Epworth Sleepiness Scale; ask about sleep attacks if on dopamine agonist

— Falls in the last 3 months; freezing episodes

— Weight (unintentional loss → swallow evaluation, depression, dyskinesias burning calories)

— Skin exam: PD has ~2× increased melanoma risk → annual dermatology screening

— ICD screening by direct questioning on every dopamine agonist visit

— Physical therapy (LSVT BIG): large-amplitude movements, balance, gait

— Speech therapy (LSVT LOUD): vocal loudness training, swallowing

— Occupational therapy: ADL adaptation, home safety, energy conservation

— Driving evaluation when cognitive or motor concerns emerge

— Group exercise: dance for PD, boxing (Rock Steady), tai chi

— Disease trajectory and expectation-setting (avoid both nihilism and false optimism)

— Sexual health and intimacy

— Workplace accommodations (FMLA, ADA, disability)

— Genetic counseling if young-onset or strong family history

— Connect to Parkinson's Foundation and Michael J. Fox Foundation resources

— Hospice eligibility includes advanced PD with significant functional decline, dysphagia, weight loss, recurrent infections

Board pearl: Annual skin exam matters: PD patients have 2- to 4-fold increased melanoma risk, independent of levodopa exposure — easy missed-screening question on Step 3.

Step 3 management: Refer to PT/speech early — not at advanced stages. Evidence supports early, intensive, amplitude-focused therapy (LSVT BIG/LOUD) for maintaining function and quality of life across the disease course.

Follow-up cadence:

At each visit, monitor:

Rehabilitation referrals:

Counseling topics:

End-of-life:

Ethical, Legal, and Patient Safety Considerations

— PD impairs reaction time, visuospatial processing, and motor execution; bradykinesia, freezing, dyskinesia, daytime sleepiness, and cognitive impairment all compromise safe driving.

— Recommend formal driving evaluation when any cognitive concern, falls, sleep attacks on dopamine agonists, or freezing emerges.

— Physician reporting requirements vary by state — some are mandatory, some permissive; know your state's law. Document discussion and recommendations in the chart.

— Capacity is decision-specific, not global. A PD patient with mild cognitive impairment may retain capacity for routine decisions but lose it for complex ones (DBS consent, financial).

— Initiate advance care planning early, while capacity intact — document healthcare proxy, code status, preferences regarding feeding tubes, DBS battery replacement, dementia-stage interventions.

— Requires capacity, realistic understanding of benefits (does not improve speech, balance, cognition, or non–levodopa-responsive symptoms; does not slow progression), and risks (hemorrhage, infection, mood/cognitive changes).

— Patients with significant dementia generally should not undergo DBS.

— Pathological gambling can devastate family finances; hypersexuality may involve coercion or risk to others.

— Physician has duty to warn the patient and (with consent) involve family; document ICD screening at every dopamine agonist visit.

— Hospital admission: missed or delayed levodopa doses cause measurable harm; medication reconciliation must specify exact clock times.

— SNF/rehab transfers: ensure receiving facility has dopaminergics on formulary and understands timing; written instructions to patient/family.

— Surgery: explicit perioperative plan; flag dopamine-blocking antiemetics and antipsychotics as contraindicated.

— Pre-test counseling; consider GINA protections (employment/insurance) and implications for biological relatives.

— Hospice and palliative integration honors patient autonomy; clarify artificial nutrition and DBS deactivation preferences in advance directives.

Step 3 management: When a 72-year-old PD patient with mild dementia is admitted and his wife reports he gambled away their retirement savings on a new pramipexole prescription, the next steps are: (1) immediate dopamine agonist discontinuation with cross-taper to levodopa, (2) capacity assessment, (3) referral to financial protection resources/adult protective services if exploitation occurred, and (4) document ICD as a documented adverse drug reaction.

Board pearl: Failure to ask about ICDs is a documentable lapse in standard of care — Step 3 ethics stems often hinge on the physician's responsibility to proactively screen for known medication harms.

Driving safety:

Decisional capacity and advance directives:

Informed consent for DBS:

Impulse control disorders and harm to self/others:

Transitions of care — high-risk moments:

Genetic testing ethics:

End-of-life:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: When you see "patient on metoclopramide for diabetic gastroparesis with new symmetric parkinsonism," the answer is almost always stop metoclopramide, not start levodopa.

Step 3 management: Memorize the three "never give in PD" antipsychotics (haloperidol, risperidone, olanzapine) and the three safe antiemetics (ondansetron, trimethobenzamide, domperidone) — repeated stem material.

TRAP = Tremor (rest), Rigidity, Akinesia/bradykinesia, Postural instability

Pathology: α-synuclein Lewy bodies; loss of dopaminergic neurons in substantia nigra pars compacta

PD tremor: 4–6 Hz, pill-rolling, asymmetric, rest, improves with action

ET tremor: 6–12 Hz, action/postural, symmetric, improves with alcohol

Hyposmia + RBD + constipation = prodromal PD triad

Strongest neuroprotective lifestyle evidence: aerobic exercise

Risk factors: age, male sex, pesticide exposure, head injury, rural living, well-water; inversely associated with smoking, coffee, and (paradoxically) higher serum urate

DaTscan: abnormal in PD and atypical parkinsonisms; normal in ET, drug-induced, psychogenic, vascular

MIBG cardiac scintigraphy: reduced in PD/DLB; preserved in MSA

First-line therapy in elderly: carbidopa-levodopa

Avoid in elderly PD: anticholinergics, amantadine (cognition); dopamine agonists if dementia/hallucinations

Causes of dopaminergic-induced psychosis: visual hallucinations most common — treat with pimavanserin or quetiapine only

Never use in PD: haloperidol, risperidone, olanzapine (problematic), metoclopramide, prochlorperazine, promethazine, ondansetron + apomorphine (severe hypotension)

DBS targets: STN (med reduction), GPi (dyskinesia control)

Parkinsonism-hyperpyrexia syndrome: from abrupt dopaminergic withdrawal → ICU, restart meds

PDD vs DLB: 1-year rule (motor first ≥1 yr = PDD; cognitive first or <1 yr = DLB)

PD with dementia: treat with rivastigmine (FDA-approved)

Aspiration pneumonia = leading cause of death

Melanoma: 2–4× increased risk → annual skin exam

Constipation: often the earliest nonmotor symptom, predating motor onset by years

Restless legs / RBD: ~80–90% of isolated RBD converts to synucleinopathy over 10–15 years

Pregnancy: levodopa preferred; amantadine teratogenic — contraindicated

Wilson disease: parkinsonism in age <40 → check ceruloplasmin, urinary copper, slit lamp

Dopa-responsive dystonia (Segawa): child with diurnal worsening, dramatic levodopa response

Board Question Stem Patterns

— 66-year-old with 18 months of right-hand resting tremor, decreased arm swing, micrographia, hyposmia.

— Answer: clinical diagnosis of PD; start carbidopa-levodopa; refer PT (LSVT BIG); screen for depression/RBD.

— Wrong answers: MRI brain (not needed if classic), DaTscan first-line (only for uncertainty), pramipexole (acceptable but suboptimal vs levodopa at this age).

— Elderly diabetic on metoclopramide develops symmetric bradykinesia.

— Answer: stop metoclopramide; reassess in months; do not start dopaminergic.

— PD patient on levodopa TID describes symptoms returning before each dose.

— Best answer: shorten interval or add entacapone (or rasagiline).

— Levodopa peak-dose chorea.

— Best answer: add amantadine ER or reduce levodopa per-dose with increased frequency.

— Visual hallucinations on dopamine agonist.

— Sequence: stop anticholinergics → amantadine → MAO-B → dopamine agonist → reduce levodopa → add pimavanserin or quetiapine.

— Never haloperidol or risperidone.

— PD patient faints standing; on pramipexole.

— Answer: nonpharm (salt, fluid, compression, HOB up), reduce dopamine agonist; add midodrine or droxidopa; avoid supine HTN.

— Early falls + vertical gaze palsy → PSP.

— Early autonomic failure + cerebellar signs → MSA.

— Cognitive decline + visual hallucinations + fluctuations → DLB.

— Alien limb + asymmetric apraxia → CBD.

— PD patient NPO for surgery.

— Answer: continue meds with sip of water; if prolonged NPO, rotigotine patch or NG levodopa; avoid metoclopramide for nausea, use ondansetron; avoid haloperidol for postop delirium, use quetiapine.

— Patient on pramipexole develops gambling problem.

— Answer: discontinue/taper dopamine agonist; transition to levodopa.

— Hospitalized PD patient whose meds were held → fever, rigidity, AMS.

— Answer: resume dopaminergics immediately, ICU care, supportive.

Board pearl: Pattern-recognize the "what's the next best step" rhythm: nearly every PD management stem is testing your knowledge of side-effect mitigation or a "do not give" medication.

Step 3 management: When in doubt, the safest answer in a PD vignette is "continue/optimize levodopa, avoid dopamine-blocking drugs, refer to PT, and screen for nonmotor symptoms."

Stem 1 — New diagnosis vignette:

Stem 2 — Drug-induced parkinsonism:

Stem 3 — Wearing-off:

Stem 4 — Dyskinesia:

Stem 5 — PD psychosis:

Stem 6 — Orthostatic hypotension:

Stem 7 — Atypical parkinsonism:

Stem 8 — Perioperative:

Stem 9 — ICD:

Stem 10 — Parkinsonism-hyperpyrexia:

One-Line Recap

Parkinson disease management is the longitudinal optimization of levodopa-based dopaminergic therapy alongside systematic screening and treatment of nonmotor complications, with vigilance for dopamine-blocking drug interactions, motor fluctuations, dyskinesias, autonomic failure, cognitive/psychiatric symptoms, and transitions-of-care hazards.

Board pearl: If a PD vignette asks "what's the most important next step," the answer is almost always either to continue/optimize levodopa, stop a dopamine-blocking offender, screen for a nonmotor symptom, or refer to PT/speech/neurology — rarely an exotic test.

Diagnosis is clinical — bradykinesia plus rest tremor or rigidity, asymmetric onset, robust levodopa response; image only to exclude mimics; DaTscan distinguishes neurodegenerative parkinsonism from ET/drug-induced/psychogenic, not subtypes of parkinsonism.

First-line therapy is carbidopa-levodopa in most patients, especially ≥65 or any cognitive concern; dopamine agonists carry ICD, sleep-attack, and orthostasis risk; anticholinergics and amantadine are problematic in the elderly; never abruptly stop dopaminergics (parkinsonism-hyperpyrexia syndrome).

Nonmotor symptoms drive disability and mortality — screen at every visit for cognition (MoCA), mood (PHQ-9), RBD, orthostasis, constipation, sialorrhea, sleep, ICDs, and hallucinations; treat psychosis with pimavanserin or quetiapine only; treat PDD with rivastigmine; aspiration pneumonia is the leading cause of death.

Safety and systems — perioperative continuation of meds, avoidance of metoclopramide/prochlorperazine/haloperidol/risperidone, exact clock-time inpatient orders, fall and bone-health prevention, annual skin exam for melanoma, early advance care planning, caregiver support, and timely referral for DBS or device-aided therapy when motor fluctuations exceed optimized medical management.