Movement Disorders Study Guide PDF

**Movement Disorders** **1. Overview of Movement Coordination Structures** **Key Brain Structures and Their Functions:** 1. **Neocortical Areas**: - Role: Higher-order **planning** and **learning**. 2. **Basal Ganglia (Extrapyramidal System)**: - Role: Coordination and modulation...

**Movement Disorders** **1. Overview of Movement Coordination Structures** **Key Brain Structures and Their Functions:** 1. **Neocortical Areas**: - Role: Higher-order **planning** and **learning**. 2. **Basal Ganglia (Extrapyramidal System)**: - Role: Coordination and modulation of movements. 3. **Cerebellum**: - Role: Coordination of voluntary movements, balance, and motor learning. 4. **Pyramidal System**: - Role: Final execution of motor commands. **2. Basal Ganglia and Movement Disorders** **Basal Ganglia Pathways:** 1. **Direct Pathway**: - Promotes movement by disinhibiting the thalamus. - In Parkinson's Disease: Loss of dopamine reduces activity → bradykinesia. 2. **Indirect Pathway**: - Suppresses movement by inhibiting the thalamus. - In Huntington's Disease: Degeneration leads to hyperkinetic movements. A diagram of a structure Description automatically generated **Disorders Related to Basal Ganglia Dysfunction:** **Disorder** **Key Features** **Mechanism** -------------------------- ---------------------------------------------- ------------------------------------------------------------------------- **Parkinson's Disease** Resting tremor, bradykinesia, rigidity Dopamine neuron loss in substantia nigra; indirect pathway dominance **Huntington's Disease** Chorea, psychiatric symptoms, dementia CAG repeat expansion; degeneration of striatal indirect pathway neurons **Wilson's Disease** Wing-beating tremor, dystonia, hepatic signs Copper accumulation in basal ganglia and other organs **3. Cerebellum: Anatomy and Associated Disorders** **Functional Divisions:** 1. **Vestibulocerebellum** (Flocculonodular Lobe): - Symptoms of Lesion: Truncal ataxia, nystagmus. 2. **Spinocerebellum** (Vermis and Intermediate Zones): - Symptoms of Lesion: Gait ataxia, intention tremor. 3. **Cerebrocerebellum** (Lateral Hemispheres): - Symptoms of Lesion: Dysdiadochokinesia, poor fine motor control. A diagram of a brain Description automatically generated **Disorders Involving the Cerebellum:** **Condition** **Key Features** **Etiology** --------------------------------------- ------------------------------------------- ------------------------------------------------- **Alcoholic Cerebellar Degeneration** Truncal ataxia, dysarthria Chronic alcohol use → damage to Purkinje cells **Friedreich's Ataxia** Gait ataxia, cardiomyopathy, diabetes GAA repeat expansion; mitochondrial dysfunction **Sensory Ataxia** Impaired proprioception, Romberg positive Loss of spinal cord inputs to the cerebellum **4. Diagnostic and Exam Techniques** **Movement and Coordination Tests:** 1. **Gait and Posture**: - Wide-based gait → Cerebellar dysfunction. - Narrow-based gait → Possible central nervous system cause. 2. **Limb Coordination**: - Dysmetria → Finger-to-nose test. - Dysdiadochokinesia → Rapid alternating movements. 3. **Eye Movements**: - Gaze-evoked nystagmus → Cerebellar lesion. - Saccadic overshoot → Cerebrocerebellum dysfunction. **Imaging and Laboratory Tests:** 1. **Bloodwork**: - Vitamin deficiencies (B12, E). - Copper and ceruloplasmin levels (Wilson's Disease). 2. **Neuroimaging**: - MRI: Detects cerebellar atrophy, basal ganglia lesions. - CT: Useful for hemorrhage, stroke. 3. **Electrodiagnostics**: - EMG/NCS: Rule out peripheral neuropathies. **5. Comprehensive Treatment Approaches** **Condition** **Management** -------------------------- ------------------------------------------------------------- **Parkinson's Disease** Levodopa, dopamine agonists, MAO-B inhibitors, DBS. **Essential Tremor** Propranolol, primidone, topiramate, gabapentin. **Huntington's Disease** Tetrabenazine, antipsychotics, supportive care. **Wilson's Disease** Copper chelation (penicillamine), zinc supplementation. **Friedreich's Ataxia** Symptomatic management; no curative treatment. **Cerebellar Ataxias** Treat underlying cause; physical therapy, adaptive devices. **6. Summary Table** **Structure** **Role in Movement** **Associated Disorders** **Symptoms** ---------------------- ---------------------------------- -------------------------------------------- ------------------------------------------ **Basal Ganglia** Modulates movement PD, Huntington's, Wilson's Bradykinesia, rigidity, hyperkinesias **Cerebellum** Coordinates movement and balance Alcoholic cerebellar degeneration, ataxias Dysmetria, gait ataxia, intention tremor **Pyramidal System** Executes voluntary movement UMN and LMN disorders Weakness, spasticity **7. Key High-Yield Points for Exams** - **Tics and Tics Syndromes**: - Non-Tourette causes: Chronic tic disorder, stimulant-induced, intellectual disability syndromes (e.g., Down syndrome). - **Pathophysiology Notes**: - Alpha-synuclein aggregation in Parkinson's leads to Lewy bodies. - CAG repeats in Huntington's lead to toxic gain of function. - **Practical Clinical Correlations**: - **Vestibular Ataxia**: Vertigo, nausea; vestibular system dysfunction. - **Sensory Ataxia**: Positive Romberg sign; proprioception loss. **Disorders/Diseases in Ataxia, Movement Disorders, and Tremor** ------------------------------------------ ---------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------- ----------------------------------------------------------------- **Disorder** **Key Features** **Pathophysiology** **Diagnosis** **Treatment** **Parkinson's Disease (PD)** Resting tremor, bradykinesia, rigidity, postural instability Loss of dopaminergic neurons in substantia nigra → Indirect pathway overactivity, direct pathway inhibition Clinical diagnosis; DAT scan for confirmation; absence of red flags Levodopa, dopamine agonists, MAO-B inhibitors, DBS **Essential Tremor** Postural/action tremor, bilateral, improves with alcohol Unknown; possible cerebellar involvement Clinical diagnosis; no specific biomarkers Propranolol, primidone, gabapentin **Huntington's Disease** Chorea, psychiatric symptoms, dementia CAG repeat expansion in HTT gene → Degeneration of indirect pathway neurons Genetic testing Tetrabenazine, antipsychotics, supportive care **Wilson's Disease** Wing-beating tremor, dystonia, hepatic and psychiatric symptoms ATP7B mutation → Copper accumulation in liver, brain, eyes Low ceruloplasmin, high urinary copper; Kayser-Fleischer rings Copper chelation (penicillamine), zinc supplementation **Progressive Supranuclear Palsy (PSP)** Early falls, axial rigidity, vertical gaze palsy Tauopathy affecting brainstem and basal ganglia Clinical diagnosis; vertical gaze palsy is a key feature Supportive care, physical therapy **Multiple System Atrophy (MSA)** Autonomic failure, poorly responsive parkinsonism Alpha-synuclein accumulation; degeneration of basal ganglia, cerebellum, and autonomic centers MRI showing cerebellar atrophy, autonomic tests Symptomatic management, treatment of autonomic dysfunction **Friedreich's Ataxia** Gait ataxia, cardiomyopathy, diabetes GAA repeat expansion in FXN gene → Mitochondrial dysfunction Genetic testing, MRI showing atrophic cervical cord Supportive care **Cerebellar Alcohol Degeneration** Truncal ataxia, dysarthria, nystagmus Chronic alcohol use → Damage to Purkinje cells, especially in anterior vermis MRI showing cerebellar atrophy Abstinence, thiamine supplementation, physical therapy **Sensory Ataxia** Proprioception loss, positive Romberg test Loss of dorsal column inputs to the cerebellum (e.g., B12 deficiency, peripheral neuropathy) Proprioceptive deficits, abnormal vibration sense Treat underlying cause **Tics (Non-Tourette)** Repetitive movements or sounds, often self-limited Dysfunction in dopamine pathways Clinical diagnosis Behavioral therapy, dopamine-depleting agents, alpha-2 agonists **Dystonia** Sustained, twisting movements, abnormal postures Imbalance in basal ganglia motor circuits Clinical diagnosis Botulinum toxin, anticholinergics **Myoclonus** Sudden, brief muscle jerks Hyperexcitability in the nervous system Clinical diagnosis; EEG for cortical myoclonus Clonazepam, valproic acid **Tardive Dyskinesia** Involuntary, repetitive movements, often orofacial Chronic dopamine receptor blockade → Dopamine receptor supersensitivity History of antipsychotic use Stop offending agent, tetrabenazine **Neuroleptic Malignant Syndrome (NMS)** Rigidity, hyperthermia, altered mental status, autonomic instability Dopamine receptor blockade Clinical diagnosis Stop offending agent, dantrolene, bromocriptine **Serotonin Syndrome** Hyperreflexia, clonus, mydriasis, encephalopathy Excess serotonergic activity Clinical diagnosis; serotonin toxicity scale Stop serotonergic agents, benzodiazepines, cyproheptadine **Corticobasal Syndrome** Asymmetric rigidity, apraxia, alien limb Tauopathy affecting cortical and basal ganglia regions Clinical diagnosis Symptomatic treatment **Restless Leg Syndrome (RLS)** Urge to move legs, worse at night, relieved by movement Dysfunction in dopaminergic pathways Clinical diagnosis Dopamine agonists, gabapentin, iron supplementation **Spinocerebellar Ataxias (SCA)** Progressive ataxia, dysarthria, nystagmus Genetic mutations (often trinucleotide repeats) → Degeneration of cerebellar and spinocerebellar tracts Genetic testing Supportive care **Cerebrotendinous Xanthomatosis** Cataracts, tendon xanthomas, cognitive decline Cholesterol metabolism defect → Accumulation of cholestanol in tissues Genetic testing, elevated cholestanol levels Chenodeoxycholic acid ------------------------------------------ ---------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------- ----------------------------------------------------------------- **Drugs in Movement Disorders and Ataxia** --------------------------------- --------------------------------------------------- ------------------------------------------------------------------------------------------------------------ --------------------------------------------- ----------------------------------------------------------- **Drug Class** **Drug Name** **Mechanism of Action** **Clinical Indications** **Key Side Effects** **Dopaminergic Agents** Levodopa + Carbidopa Levodopa: Dopamine precursor; Carbidopa: Inhibits peripheral decarboxylase, increasing CNS levodopa levels Parkinson's Disease Dyskinesias, nausea, orthostatic hypotension Dopamine Agonists (e.g., pramipexole, ropinirole) Directly stimulate dopamine receptors Parkinson's Disease, Restless Legs Syndrome Impulse control disorders, hallucinations, sleep attacks **MAO-B Inhibitors** Selegiline, Rasagiline Inhibit monoamine oxidase B → Prevent dopamine breakdown Parkinson's Disease Insomnia, nausea, risk of serotonin syndrome **COMT Inhibitors** Entacapone, Tolcapone Inhibit catechol-O-methyltransferase → Prolong effect of levodopa Parkinson's Disease Diarrhea, liver toxicity (Tolcapone) **Anticholinergics** Benztropine, Trihexyphenidyl Block muscarinic receptors → Reduce acetylcholine-mediated tremor Parkinsonian Tremor Dry mouth, constipation, cognitive impairment **NMDA Receptor Antagonist** Amantadine Blocks NMDA receptors → Reduces glutamate excitotoxicity; increases dopamine release Parkinson's Disease (dyskinesias) Livedo reticularis, hallucinations, peripheral edema **Dopamine-Depleting Agents** Tetrabenazine, Deutetrabenazine Inhibit VMAT2 → Decrease dopamine release Huntington's Disease, Tardive Dyskinesia Depression, sedation, Parkinsonism **Antipsychotics** Quetiapine, Clozapine Dopamine receptor blockade; clozapine also blocks serotonin receptors Psychosis in Parkinson's Disease Sedation, metabolic syndrome, agranulocytosis (Clozapine) **Beta-Blockers** Propranolol Non-selective beta-adrenergic blockade Essential Tremor Bradycardia, hypotension, fatigue **Anticonvulsants** Primidone Metabolized to phenobarbital → Enhances GABA-mediated inhibition Essential Tremor Sedation, ataxia, nausea Gabapentin, Pregabalin Modulate calcium channels → Reduce excitatory neurotransmitter release Essential Tremor, Restless Legs Syndrome Sedation, dizziness, weight gain **Chelating Agents** Penicillamine Binds free copper → Promotes excretion Wilson's Disease Hypersensitivity reactions, nephrotoxicity **Zinc Supplementation** Zinc acetate, Zinc sulfate Competes with copper for intestinal absorption Wilson's Disease GI upset **Cholesterol-Lowering Agents** Chenodeoxycholic acid Replaces bile acids → Reduces cholestanol accumulation Cerebrotendinous Xanthomatosis GI upset, diarrhea **Benzodiazepines** Clonazepam, Lorazepam Enhance GABA-A receptor activity → CNS depression Myoclonus, Restless Legs Syndrome Sedation, dependency, respiratory depression **Serotonin Antagonist** Cyproheptadine Blocks serotonin receptors Serotonin Syndrome Sedation, weight gain **Calcium Channel Blockers** Acetazolamide Inhibits carbonic anhydrase → Reduces neuronal excitability Episodic Ataxia Electrolyte imbalances, paresthesia --------------------------------- --------------------------------------------------- ------------------------------------------------------------------------------------------------------------ --------------------------------------------- -----------------------------------------------------------  **Imaging Modalities and Findings in Movement Disorders** -------------------------------------------------------- ----------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------- ----------------------------------------- ------------------------------------------------------- **Modality** **Description** **Typical Uses in Movement Disorders** **Key Findings** **Advantages** **Limitations** **MRI (Magnetic Resonance Imaging)** Uses magnetic fields and radio waves to create detailed images of soft tissues. Structural evaluation of the brain, particularly basal ganglia and cerebellum. \- Atrophy in **Huntington's Disease** (caudate nucleus) High resolution, no ionizing radiation Expensive, less useful for dynamic imaging \- Iron deposition in **Parkinson's Disease** (susceptibility-weighted imaging) \- Cerebellar atrophy in **Friedreich's Ataxia** **CT (Computed Tomography)** Uses X-rays to create cross-sectional images of the brain. Rapid evaluation for acute conditions such as stroke or hemorrhage causing movement disorders. \- Hyperdense basal ganglia in **hemorrhagic stroke** Fast, widely available Limited soft tissue contrast, uses ionizing radiation \- Calcifications in basal ganglia in **metabolic disorders** **DAT Scan (Dopamine Transporter Imaging)** Nuclear medicine scan using radiolabeled tracers that bind to dopamine transporters in the basal ganglia. Differentiating **Parkinson's Disease** from atypical or drug-induced parkinsonism. \- Reduced tracer uptake in **Parkinson's Disease** Specific for dopamine system evaluation Limited availability, radiation exposure \- Normal uptake in **essential tremor** **PET Scan (Positron Emission Tomography)** Measures metabolic activity of the brain using radiolabeled tracers. Research and advanced diagnostics for neurodegenerative conditions. \- Hypometabolism in **Parkinson's Disease** or **PSP** Functional imaging High cost, radiation exposure \- Altered glucose metabolism in **Huntington's Disease** **SPECT (Single Photon Emission Computed Tomography)** Nuclear medicine scan providing functional imaging of cerebral blood flow. Evaluating perfusion abnormalities in neurodegenerative diseases. \- Hypoperfusion in basal ganglia and frontal lobes in **Parkinson's Disease** Functional imaging Limited spatial resolution **Ultrasound (Transcranial Doppler)** Uses high-frequency sound waves to assess blood flow in cerebral vessels. Detecting **hyperechogenicity** of the substantia nigra in Parkinson's Disease. \- Substantia nigra hyperechogenicity in **Parkinson's Disease** Non-invasive, low cost Operator-dependent, limited structural information **SWI (Susceptibility Weighted Imaging)** MRI sequence sensitive to magnetic properties of tissue. Evaluating iron deposition in basal ganglia. \- Increased iron deposition in **Parkinson's Disease** and **PSP** Enhanced detection of mineral deposits Limited availability in all centers -------------------------------------------------------- ----------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------- ----------------------------------------- ------------------------------------------------------- **Typical Imaging Findings for Common Movement Disorders** ------------------------------------------ ---------------------- -------------------------------------------------------------------------------------------- **Disorder** **Imaging Modality** **Findings** **Parkinson's Disease** MRI, DAT Scan, SWI Iron deposition in substantia nigra (SWI); Reduced dopamine transporter uptake (DAT scan). **Huntington's Disease** MRI, PET Caudate nucleus and putamen atrophy (MRI); Frontal and basal ganglia hypometabolism (PET). **Wilson's Disease** MRI T2 hyperintensity in basal ganglia (face of the giant panda sign). **Friedreich's Ataxia** MRI Cerebellar and cervical spinal cord atrophy. **Progressive Supranuclear Palsy (PSP)** MRI, PET Midbrain atrophy (hummingbird sign); Cortical and basal ganglia hypometabolism (PET). **Essential Tremor** MRI, DAT Scan Normal MRI; Normal dopamine transporter uptake on DAT scan. **Multiple System Atrophy (MSA)** MRI Hot cross bun sign in the pons; Cerebellar atrophy in MSA-C variant. ------------------------------------------ ---------------------- -------------------------------------------------------------------------------------------- **Summary of Modalities for Comparison** - **MRI**: Best for structural abnormalities (e.g., atrophy, iron deposition). - **DAT Scan**: Best for differentiating Parkinson's from mimics. - **PET/SPECT**: Best for functional evaluation (e.g., metabolism, perfusion). - **Ultrasound**: Rapid and inexpensive for initial evaluation of Parkinsonian changes. **Recognition of Ataxia and Common Movement Disorders** ---------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------ **Disorder/Movement Type** **Key Features** **Pathophysiology** **Associated Conditions** **Key Distinguishing Features** **Ataxia** Imbalance, incoordination of gait, limbs, or speech. Dysmetria, intention tremor, dysdiadochokinesia, wide-based gait, difficulty tandem walking. Cerebellar dysfunction; may involve spinocerebellar or cerebrocerebellar pathways. Cerebellar stroke, multiple sclerosis, alcohol-induced cerebellar degeneration, Friedreich's ataxia. Negative Romberg test (if cerebellar). Positive Romberg test suggests sensory ataxia. **Tremor** Involuntary, rhythmic oscillations of a body part. Types: resting, postural, action, intention. Abnormal oscillatory activity in motor circuits, often involving the basal ganglia or cerebellum. Parkinson's Disease (resting tremor), Essential Tremor (action/postural tremor). Resting tremor → Parkinson's. Intention tremor → Cerebellar disorders. Postural tremor → Essential Tremor. **Tics** Sudden, repetitive, stereotyped movements or vocalizations. Can be suppressed temporarily. Dysfunction in dopamine pathways in basal ganglia. Tourette Syndrome, chronic tic disorder, intellectual disability (e.g., Down syndrome). Premonitory urge; voluntary suppression possible. **Athetosis** Slow, writhing movements, typically of the distal limbs. Basal ganglia dysfunction; often affects the indirect pathway. Cerebral palsy, Huntington's Disease. Writhing, continuous movement of fingers, hands, or toes. **Chorea** Rapid, irregular, flitting movements of multiple body parts. Degeneration of indirect pathway neurons in basal ganglia. Huntington's Disease, Wilson's Disease, Sydenham's Chorea (post-streptococcal). Jerky, unpredictable movements; often flowing from one body part to another. **Ballism** Violent, flinging, large-amplitude movements, usually unilateral. Lesion in the subthalamic nucleus, leading to reduced inhibition of the thalamus. Hemiballismus (typically caused by stroke). High-amplitude, proximal limb movements; unilateral. **Dystonia** Sustained or intermittent muscle contractions causing abnormal postures or repetitive movements. Dysfunction in basal ganglia circuits; may involve co-contraction of agonist and antagonist muscles. Focal dystonia (e.g., cervical dystonia), generalized dystonia, drug-induced dystonia (e.g., antipsychotics). Twisting or sustained abnormal posture; exacerbated by specific actions or tasks. **Bradykinesia** Slowness of movement; difficulty initiating voluntary movements. Reduced dopamine in the basal ganglia, leading to impaired direct pathway activity. Parkinson's Disease, Progressive Supranuclear Palsy. Reduced amplitude of movements; slow gait initiation; reduced facial expressions (hypomimia). ---------------------------- --------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------ --------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------ **Summary of Key Recognition Features:** 1. **Ataxia**: Often cerebellar; gait imbalance and limb incoordination. 2. **Tremor**: Context-dependent (resting, action, intention). 3. **Tics**: Suppressible, stereotyped, with a premonitory urge. 4. **Athetosis**: Writhing movements, common in cerebral palsy. 5. **Chorea**: Irregular, jerky, rapid movements; associated with Huntington's. 6. **Ballism**: Unilateral, large-amplitude flinging movements; often stroke-related. 7. **Dystonia**: Sustained contractions; twisting postures. 8. **Bradykinesia**: Hallmark of Parkinson's Disease; slowness and difficulty with voluntary motion. **Parkinson's Disease (PD)** **1. Clinical Features of Parkinson's Disease** PD is characterized by a combination of **motor** and **non-motor** symptoms. Symptoms typically begin asymmetrically and gradually progress. **Motor Features (Cardinal Symptoms)**: 1. **Bradykinesia**: Slowness of movement; difficulty initiating and executing voluntary movements. 2. **Rigidity**: Increased resistance to passive movement (lead-pipe rigidity, cogwheeling). 3. **Resting Tremor**: Often described as a \"pill-rolling\" tremor, usually beginning unilaterally. 4. **Postural Instability**: Late-stage feature; increased risk of falls. **Non-Motor Features**: 1. **Cognitive**: - Impaired executive function and memory. - Parkinson's Disease Dementia: Typically develops late in the disease course. 2. **Psychiatric**: - Depression and anxiety. - Hallucinations and psychosis (can be medication-induced or disease-related). 3. **Autonomic**: - Orthostatic hypotension. - Detrusor hyperactivity causing urinary urgency and frequency. - Erectile dysfunction. 4. **Olfactory**: - Hyposmia or anosmia (early symptom, often pre-diagnostic). 5. **Gastrointestinal**: - Constipation due to slowed gastrointestinal motility. 6. **Urologic**: - Nocturia and incomplete bladder emptying. 7. **Speech and Swallowing**: - Hypophonia (soft speech). - Dysphagia, leading to aspiration risks. **2. Causes of Extrapyramidal Symptoms with Parkinsonian Features (Non-PD)** 1. **Drug-Induced Parkinsonism**: - Common culprits: Antipsychotics (e.g., haloperidol, risperidone), antiemetics (e.g., metoclopramide). - Typically bilateral onset and may improve upon discontinuation. 2. **Atypical Parkinsonian Syndromes**: - **Progressive Supranuclear Palsy (PSP)**: Early falls, vertical gaze palsy, axial rigidity. - **Multiple System Atrophy (MSA)**: Autonomic failure, cerebellar signs, poor levodopa response. - **Corticobasal Degeneration (CBD)**: Asymmetric rigidity, apraxia, alien limb phenomenon. 3. **Other Causes**: - **Vascular Parkinsonism**: Lower body parkinsonism, gait disturbance, multiple small infarcts. - **Toxic and Metabolic Causes**: Manganese toxicity, Wilson's disease, hypothyroidism. - **Postencephalitic Parkinsonism**: Rare, historically linked to the influenza epidemic. - **Normal Pressure Hydrocephalus (NPH)**: Triad of gait disturbance, urinary incontinence, and dementia. **3. Pharmacologic and Non-Pharmacologic Management of PD** **Pharmacologic Management**: 1. **Dopaminergic Therapy**: - **Levodopa-Carbidopa**: Most effective for motor symptoms. - Carbidopa inhibits peripheral breakdown of levodopa, reducing side effects like nausea. - Side effects: Dyskinesias, motor fluctuations (wearing-off effect). 2. **Dopamine Agonists**: - Examples: Pramipexole, ropinirole. - Useful in early disease or younger patients. - Side effects: Impulse control disorders (e.g., gambling, hypersexuality), sleep attacks, hallucinations. 3. **MAO-B Inhibitors**: - Examples: Selegiline, rasagiline. - Mechanism: Inhibit dopamine breakdown in the CNS. - Side effects: Insomnia, nausea, potential serotonin syndrome with SSRIs. 4. **COMT Inhibitors**: - Examples: Entacapone, tolcapone. - Mechanism: Prolongs levodopa's effect by inhibiting peripheral breakdown. - Side effects: Diarrhea, liver toxicity (tolcapone). 5. **Amantadine**: - Mechanism: NMDA receptor antagonist; reduces dyskinesias. - Side effects: Livedo reticularis, hallucinations, peripheral edema. 6. **Anticholinergics**: - Examples: Benztropine, trihexyphenidyl. - Useful for tremor. - Side effects: Dry mouth, constipation, cognitive impairment. **Non-Pharmacologic Management**: 1. **Exercise and Physical Therapy**: - Improve mobility, balance, and reduce fall risk. 2. **Speech Therapy**: - Address hypophonia and dysphagia. 3. **Dietary Adjustments**: - High-fiber diet for constipation; adequate hydration. 4. **Deep Brain Stimulation (DBS)**: - Indicated in advanced disease with motor fluctuations or refractory tremor. **4. Motor Complications and Non-Motor Side Effects of PD Medications** **Motor Complications**: 1. **Wearing-Off Effect**: - Symptoms return as levodopa effect diminishes before the next dose. - Management: Shorten dosing intervals, add COMT inhibitors or MAO-B inhibitors. 2. **Dyskinesias**: - Involuntary, erratic movements associated with peak levodopa levels. - Management: Reduce levodopa dose; consider amantadine. **Non-Motor Side Effects**: 1. **Psychiatric**: - Hallucinations and psychosis (especially with dopamine agonists). - Management: Reduce offending drug; use quetiapine or clozapine if needed. 2. **Autonomic**: - Orthostatic hypotension (dopaminergic agents). - Management: Increase fluid/salt intake, fludrocortisone. 3. **GI Symptoms**: - Nausea and vomiting (levodopa). - Management: Take with meals or use carbidopa. A diagram of a disease Description automatically generated **Tremor Classification and Features** ----------------------------------- ------------------------------------------------------------------------------------------------ ------------------------------------------ -------------------------------------------------------------------------------------- ------------------------ ------------------------------------------------------- **Tremor Type** **Description** **Ways to Test** **Pathophysiology** **Frequency** **Examples/Associations** **Resting Tremor** Occurs when the body part is at rest and supported; decreases with voluntary movement. Observe patient at rest. Dysfunction in the basal ganglia (e.g., loss of dopamine in substantia nigra). 4--6 Hz Parkinson's Disease **Postural Tremor** Occurs when maintaining a position against gravity (e.g., arms outstretched). Ask patient to extend arms in front. Possible cerebellar or essential tremor mechanism; enhanced by physiological stress. 6--10 Hz Essential Tremor, anxiety, hyperthyroidism **Action Tremor** General term for tremors occurring during voluntary movement. Finger-to-nose test. Cerebellar dysfunction or peripheral enhancement (e.g., from drugs or toxins). Variable Cerebellar disease **Intention Tremor** Subtype of action tremor; amplitude increases as the target is approached. Finger-to-nose or heel-to-shin test. Cerebellar dysfunction, particularly in lateral cerebellar hemispheres. Low frequency Cerebellar lesions, MS **Kinetic Tremor** Occurs during any movement (not task-specific). Observe during general movement tasks. Similar mechanisms to action tremor. Variable Essential Tremor **Task-Specific Tremor** Tremor occurs only during specific activities (e.g., writing). Writing or other specific tasks. Maladaptive brain-muscle feedback mechanisms. Variable Primary writing tremor **Physiological Tremor** Low-amplitude tremor present in everyone; exaggerated by stress, fatigue, or medications. Rest and postural testing under stress. Normal oscillatory activity in muscles; enhanced by adrenergic activity. 8--12 Hz Anxiety, stimulants, hyperthyroidism **Enhanced Physiological Tremor** Exaggeration of physiological tremor, often due to a specific trigger (e.g., drugs, caffeine). Similar to physiological tremor testing. Adrenergic or central nervous system hyperexcitability. 8--12 Hz Caffeine, drugs, metabolic derangements **Orthostatic Tremor** Rare, high-frequency tremor occurring in legs while standing; resolves when sitting. Observe while standing. Central oscillator dysfunction; unclear etiology. 14--16 Hz Orthostatic Tremor Syndrome **Holmes Tremor** Low-frequency tremor present at rest, posture, and action. Observe at rest and during movements. Lesions affecting red nucleus, cerebellum, and thalamus (\"rubral tremor\"). \