Week 9: Neurodegenerative, Dementia, Urinary

Parkinson’s Disease

• progressive, gradual neurological degenerative disorder of the brain

Parkinson’s Disease Patho

• Parkinson's disease results from death of dopamine-producing neurons in the substantia nigra of the brain

  • motor symptoms appear when approximately 50% of dopaminergic neurons in the substantia nigra are lost

• loss of dopamine in the basal ganglia

• dopamine depletion in the corpus striatum causes motor symptoms

Parkinson’s Types

• primary (idiopathic)

• secondary

  • CNS infection

  • tumor growths in the brain

  • cerebral ischemia

  • antipsychotic medications

Parkinson’s Stages

• Stages 1-2: starts in the medulla and olfactory bulb

• Stages 3-4: progresses to substantia nigra

• Stages 5-6: then to cerebral cortex

Parkinson’s Cardinal Motor Symptoms

1. Tremor: resting tremor, unilateral, “pill-rolling” motion

2. Rigidity: cogwheel rigidity (ratcheting) or lead pipe rigidity (constant)

3. Akinesia/bradykinesia - slowness of movement, decreased manual dexterity

4. Postural instability - shuffling gait, stooped posture, balance problems

   • (TRAP)

Parkinson’s: Other Motor Signs

• masked face (flat facial expression)

• decreased spontaneous movements

• shuffling gait with short steps

• festinating gait (involuntary acceleration)

• freezing episodes (sudden inability to move)

Parkinson’s: Diagnosis

• primarily history and physical exam

• requires bradykinesia PLUS rigidity and/or tremor

• symptoms typically start unilaterally/asymmetrically

• dramatic response to levodopa supports diagnosis

Carbidopa-Levodopa: Drug Type

• dopamine replacement

• gold standard and more effective treatment for Parkinson’s motor symptoms

• does NOT slow disease progression

  • only treats symptoms

Levodopa

• metabolic precursor of dopamine

• crosses blood-brain barrier (dopamin itself cannot)

• converted to dopamine in the brain

• replaces depleted dopamine to relieve symptoms

Carbidopa

• inhibits peripheral decarboxylation of levodopa

• allows more levodopa to reach the brain

Carbidopa-Levodopa: Nursing Considerations

• do NOT crush or chew extended-release formulations

• **high-protein meals can decrease formulations

• may take with food if GI upset occurs

  • but absorption may be reduced

Carbidopa-Levodopa: Side Effects

• Early: N/V, **orthostatic hypotension, dizziness

• Later: dyskinesia (erratic movements), motor fluctuations

• “wearing off” phenomenon: symptoms return before next dose

• **“on-off” phenomenon: unpredictable swings between mobility and immobility

• hallucinations, confusion (especially in elderly)

• monitor for impulse control disorders

Carbidopa-Levodopa: Abrupt Discontinuation

• can cause neuroleptic malignant syndrome-like reactions

• high fever

• severe muscle rigidity

• altered mental status

• autonomic instability

Carbidopa-Levodopa: Patient Consideration

• may take several weeks to see full benefit

• do not stop medication abruptly

• change positions slowly (orthostatic hypotension risk)

• report involuntary movements, mood changes, hallucinations

• medication effectiveness may decrease over time (years of use)

• protein spacing strategies may be needed if "wearing off" occurs

Dementia

• chronic, progressive decline in cognitive function caused by damage to neurons and neural networks in the brain

• NOT a normal part of aging

Alzheimer’s Disease

• (40-45%), most common

• insidious onset with episodic memory loss (forgetting recent events, repeating questions)

• accumulation of beta-amyloid plaques and tau tangles

• gradual progression

• more common in women >65

• life expectancy 4-8 years after diagnosis

Vascular Dementia

• (14-15%), second most common

• generally localized to the area of vessel disease

• stepwise decline with abrupt worsening after strokes/TIAs

• may have focal neurologic deficits (weakness, gait changes)

• risk factors: HTN , diabetes, atrial fibrillation, smoking

• more common in men >65

Lewy Body Dementia

• (4-6%)

• visual hallucinations, fluctuating cognition, REM sleep behavior disorder, Parkinsonian features (rigidity, bradykinesia)

• extreme sensitivity to antipsychotics (can cause neuroleptic malignant syndrome)

• more common in men 70-85 years

• LBD starts with cognitive decline, hallucinations, or behavioral issues, with motor symptoms developing later

  • Parkinson’s begins with motor problems

Frontotemporal Dementia

• (1%)

• characterized by focal degeneration

• early onset (often <60 years, 45-65 yo)

• personality/behavior changes (disinhibition, apathy, socially inappropriate behavior, loss of empathy)

• language variant with progressive aphasia

• memory relatively preserved early

• rapid progression

Stages of Alzheimer’s Disease

1. Initial: short-term memory loss

2. Moderate: global cognitive impairment

   1. language, problem solving, disorientation, inability to carry on daily activities

3. Severe: loss of ability to respond to the environment, requires total care, bedridden

Donepezil

• acetylcholinesterase inhibitor

  • reversibly inhibits the enzyme acetylcholinesterase, which breaks down acetylcholine in the brain

• MOA: increases cholinergic transmission (may improve memory)

• does NOT alter the course of underlying disease or slow neurodegeneration - only treats symptoms

Donepezil: Side Effects

• Common: N/V, insomnia/vivid dreams, muscle cramps, fatigue, bruising

• Serious: bradycardia, GI bleeding risk (increased gastric acid), weight loss

Donepezil: Nursing Priorities

• monitor HR/rhythm and weight regularly

• observe for GI side effects at initiation and dose increases

• contraindicated in bradycardia: caution with CV diseases

• education: it treats symptoms only, report dizziness/fainting/slow heartbeat immediately

Memantine

• MOA: NMDA receptor antagonist (blocks NMDA receptors)

  • limits overstimiulation of nerves

• treats symptoms only, does NOT slow disease progression

• only for moderate to severe Alzheimer's disease

  • can be used alone or combined with cholinesterase inhibitors

Memantine: Considerations

• Side Effects: headache, dizziness, constipation, confusion

• Advantages: much fewer GI and cardiac side effects than cholinesterase inhibitors

• Caution: use caution in CV disease, seizures, severe hepatic/renal impairment

• raises urine pH (UTIs)

Lecanemab

• Use: mild cognitive impairment/dementia

  • NOT a cure

• MOA: removes beta amyloid plaque from the brain

• can cause brain micromorrhages → can lead to death

Multiple Sclerosis

• chronic, immune-mediated, inflammatory disease of the central nervous system (CNS) causing demyelination, axonal injury, and neurodegeneration

Multiple Sclerosis: Affect + Characterized

• affects brain, spinal cord, optic nerves

• characterized by relapses and/or progressive decline

• leads to slowed or blocked nerve conduction

Multiple Sclerosis: Core Pathophysiology

1. Autoimmune Response

• T-cells and B-cells cross the blood-brain barrier

• triggers inflammation → releases cytokines,antibodies, and complement

• targets myelin sheath and oligodendrocytes

2. Result

• demyelination

• loss of oligodendrocytes → impaired remyelination

• formation of MS plaques in white matter

MS: Demyelination

• myelin damage → slowed nerve conduction

• conduction block → sensory, motor, visual deficits

MS: Axonal Damage

• inflammatory environment injuries axons

• leads to irreversible disability over time

MS: Connecting Patho + Symptoms

• Optic Neuritis: demyelination of optic nerve

• Fatigue: cytokine burden + neural injury

• Spasticity/Weakness: motor tract lesions

• Ataxia/Tremor: cerebellar involvement

• Bladder Dysfunction: spinal cord lesions

• Cognitive Changes: cortical and subcortical atrophy (changes in white matter)

MS: Classic Presentations

• unilateral optic neuritis

• partial myelitis (muscle weakness)

• cognitive impairment

MS: High-Efficacy Options

• natalizumab (anti-α4 integrin)

  • blocks immune cells from crossing the blood-brain barrier

  • prevents them from entering the CNS and causing damage

• ocrelizumab/ofatumumab (anti-CD20 B-cell depletion)

  • deplete B cells (which contribute to MS inflammation)

• alemtuzumab (anti-CD52)

  • broadly depletes T and B lymphocytes

  • causes long-lasting immune suppression

• cladribine (purine analog)

  • selectively reduces lymphocytes (T and B cells)

MS: Acute Relapse Treatment

• high-dose corticosteroids

• IV methylprednisolone or oral prednisone

• speeds up recovery but doesn’t affect long-term disability

Multiple Sclerosis: Considerations

• monitor for infection risk with immunosuppressants

• young adults aged 20-30 years at onset

  • women affected 3:1 to men

• heat sensitivity, avoiding tigger

• regular MRI monitoring (6-12 months)

  • assesses disease activity

• symptomatic management: spasticity, bladder dysfunction, fatigue, pain, depression

Myasthenia Gravis (MG)

• chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness that worsens with activity and improves with rest

• affects the neuromuscular junction (NMJ) — not the muscle, not the nerve, but the communication between them

Myasthenia Gravis (MG): Patho

• autoantibodies target acetylcholine (ACh) receptors on the postsynaptic membrane

• ↓ # of available ACh receptors

• ↓ strength and efficiency of neuromuscular transmission

Myasthenia Gravis (MG): Muscles Most Affected

• ocular

• bulbar

• respiratory

• proximal limb

Myasthenia Gravis (MG): Ocular Symptoms

• initial presentation

• asymmetric ptosis (eyelid dropping)

• diplopia (double vision)

Myasthenia Gravis (MG): Bulbar Symptoms

• reduced facial expression

• dysphagia

• difficulty chewing

• dysarthria (impairs coordination of muscles used for speaking)

Myasthenia Gravis (MG): Limb Weakness Presentation

• proximal > distal

• difficulty climbing stairs

• difficulty lifting arms

• difficulty rising from seated position

Myasthenia Gravis (MG): Respiratory Muscle Weakness

• can lead to life-threatening myasthenic crisis (~15% of patients)

• severe respiratory muscle weakness leads to acute respiratory failure

• requiring immediate mechanical ventilation or intensive care

Myasthenia Gravis (MG): Key Features

• normal reflexes

• no sensory involvement

• weakness worsens with sustained activity

Pyridostigmine

• Acetylcholinesterase Inhibitor

• MOA: acetylcholinesterase inhibitor that increases acetylcholine at the neuromuscular junction

• Use: first-line symptomatic treatment for myasthenia gravis

Pyridostigmine: Key Points

• symptomatic treatment for MG

  • helps with daytime fatigue

  • must be given on time

  • short half-life → multiple daily doses

• give 30-60 minutes before meals

Myasthenic Crisis

• life-threatening complication of myasthenia gravis

• respiratory failure requiring mechanical ventilation due to respiratory muscle weakness; medical emergency

• triggers: surgery, meds, stress, pregnancy

• warning signs: increasing dyspnea, weak cough, difficulty handling secretions, declining vital capacity

Cholinergic Crisis

• SLUDGE

• Sweating & Salivation

• Lacrimation

• Urination

• Diarrhea

• Gastrointestinal cramps and pain

• Emesis

Cholinergic Crisis vs Myasthenic Crisis

• both life-threatening respiratory failures in Myasthenia Gravis

• both cause weakness

• cholinergic crisis has cholinergic symptoms (SLUDGE)

Guillain-Barre Syndrome (GBS)

• an acute, immune-mediated polyneuropathy causing rapid onset, ascending muscle weakness

• autoantibodies attack peripheral nerve components following infection

• cross-reactive immune response

Guillain-Barre Syndrome (GBS): Key Features

• affects peripheral nervous system

• often triggered by a preceding infection (Campylobacter jejuni)

  • symptoms begin 1-6 weeks after infection

  • other triggers: Cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, influenza, Zika virus, COVID-19

• *medical emergency due to risk of respiratory failure

Guillain-Barre Syndrome (GBS): Classic Presentation

• progressive, ascending, symmetric weakness starting in legs and moving upward; reaches nadir within 4 weeks (usually 2 weeks)

Guillain-Barre Syndrome (GBS): Hallmark

• weakness with areflexia or hyporeflexia

  • (absent/decreased deep tendon reflexes)

Guillain-Barre Syndrome (GBS): Respiratory Failure

• occurs in 20-30% of patients

• requires mechanical ventilation

• most dangerous complication

• may need intubation rapidly

Guillain-Barre Syndrome (GBS): Sensory Symptoms

• numbness

• paresthesias

• pain in limbs (often precedes weakness)

Guillain-Barre Syndrome (GBS): Cranial Nerve Involvement

• facial weakness (bilateral facial palsy)

• bulbar weakness (dysphagia, dysarthria)

• ophthalmoplegia

Guillain-Barre Syndrome (GBS): Clinical Progression

• ascending weakness: feet→legs→trunk→arms→face

• course of illness:

1. Acute (1-4 weeks): rapid symptom progression

2. Plateau (days-weeks)

3. Recovery (months-years): remyelination begins

• majority fully recover, but fatigue/neuropathic pain may persist

Guillain-Barre Syndrome (GBS): Treatment

• no cure and no role for steroids

• IVIG

• plasma exchange

Guillain-Barre Syndrome (GBS): IVIG

• first line

• infusion of antibodies → blocks harmful autoimmune antibodies

• slows or halts progression

• works best if started within 2 weeks of symptoms onset

Guillain-Barre Syndrome (GBS): IVIG Side Effects

• headache

• fever

• thrombosis risk

  • makes blood thicker

• aseptic meningitis (rare)

Urinary Retention

• inability to fully empty the bladder due to impaired detrusor contraction or outflow obstruction

• seen in MS, Parkinson’s, spinal cord injury, diabetic neuropathy, advanced dementia

Normal Voiding: Storage Phase

• sympathetic nervous system increases detrusor muscle tone + somatic external urethral sphincter tone to maintain continence

Normal Voiding: Voiding Phase

• parasympathetic activation causes detrusor contraction + sphincter relaxation, coordinated by pontine micturition center in brainstem

Acute Urinary Retention (AUR)

• sudden inability to void

• painful, distended bladder

• urologic emergency

Chronic Urinary Retention

• post-void residual (PVR) >300 mL on two occasions persisting ≥6 months

Symptoms of Retention

• dribbling or overflow incontinence

• hesitancy

• weak stream

• sensation of incomplete emptying

• recurrent UTIs

Urine Retention Causes

1. Obstructive Causes (most common)

• benign prostatic hyperplasia

• prostate cancer, urethral structure, bladder stones, fecal impaction, pelvic organ prolapse

2. Neurogenic Causes

• spinal cord injury, MS, diabetic neuropathy, stroke, Parkinson'‘s

3. Sacral cord or cauda equina lesions → areflexic/flaccid bladder (detrusor cannot contract)

Urinary Incontinence

• overactive detrusor muscle causing urge, frequency, and incontinence

• empties too often or involuntarily

Oxybutynin

• Anticholinergics

• block parasympathetic detrusor contraction

• Use: urinary incontinence, overactive bladder

Tamsulosin

• Alpha-adrenergic Agonists

• Use: treats incontinence

• increase sphincter tone

• strengthen the urethral sphincter

Urinary Retention: Clinical Manifestations

• Acute: Suprapubic pain, distended bladder, inability to void, restlessness

• Chronic: May be painless; overflow incontinence (dribbling), weak stream, incomplete emptying, recurrent UTIs

• Complications: Hydronephrosis, renal insufficiency, bladder diverticula, bladder stones, recurrent UTIs

Overactive Bladder (OAB)

• syndrome of urinary urgency, frequency, nocturia, ± urge incontinence without infection or other pathology

Anticholinergics/Antimuscarinics

• block parasympathetic M2/M3 receptors → decrease detrusor contraction

• Use: urinary incontinence, overactive bladder

• Side effects: dry mouth, constipation, dry eyes, cognitive impairment

• Contraindicated in: Uncontrolled narrow-angle glaucoma, urinary retention, gastric retention