Neurodegenerative Movement Disorders

• Parkinson's, Huntington's, and Alzheimer's are neurodegenerative diseases
• These diseases feature a progressive loss of neuronal function in specific CNS parts
• Neurodegenerative disease symptoms do not reflect typical age-related neuron loss
• They result from an underlying pathologic process
• The specific causes of these diseases are unknown
• Heredity, autoimmunity, and environmental factors may play a role
• Drug therapy options remain limited for neurodegenerative diseases

Types of Movement Disorders

• Tremor: Rhythmic oscillatory movement around a joint
• Chorea: Irregular, unpredictable, involuntary muscle jerks
• Athetosis: Slow, writhing movements
• Dystonia: Sustained abnormal postures
• Tics: Sudden, coordinated abnormal movements
  • Tics are usually repetitive
  • Common in children
  • Can be briefly suppressed voluntarily
  • Examples include repetitive sniffing and shoulder shrugging

Neuroanatomical Basis

• Movement disorders are often linked to disturbances in the basal ganglia
• The basic circuitry of movement involves three interacting neuronal loops: one connecting the cortex to the basal ganglia, another linking the basal ganglia to the thalamus, and a feedback loop returning to the cortex.
• Precise function is not fully understood
• Specific symptoms cannot be definitively linked to specific anatomical sites

Parkinsonism and Parkinson's Disease

• Cardinal motor symptoms include primary characteristics of rigidity, Bradykinesia and tremor
• Bradykinesia, characterized by a marked slowness in movement, is a pivotal criterion for diagnosing Parkinson's Disease, as it distinctly differentiates this condition from other movement disorders.
• Postural instability is a primary characteristic of Parkinson's Disease, manifesting as difficulty in maintaining balance and orientation, which significantly increases the risk of falls and contributes to overall mobility challenges in affected individuals.
• Additional motor features may also encompass focal dystonia, characterized by sustained muscle contractions in specific body areas, leading to abnormal postures or movements.

Non-Motor Symptoms

• Cognitive/Psychiatric symptoms include cognitive decline(common in advanced disease), depression, anxiety, personality changes, and Apathy ( characterized by a lack of interest, enthusiasm, or concern, often seen in individuals with neurodegenerative diseases)
• Autonomic Dysfunction symptoms include sphincter and sexual dysfunction
  • Dysphagia, or difficulty swallowing, is a common symptom in various neurological disorders, including Parkinson's Disease. It can lead to choking, which is a serious risk, as it poses a threat to the patient's airway.
  • Sweating abnormalities
  • Sialorrhea, also known as excessive salivation or drooling, refers to the production of an abnormally large amount of saliva.
  • Blood pressure regulation issues
• Other Manifestations include fatigue, sleep disorders, and sensory complaints and pain

Pathophysiology

• Parkinson's Disease involves issues in the basal ganglia
• Dopamine production in the substantia nigra pars compacta is disrupted

Preclinical Phase

• Early warning signs include Hyposmia (reduced sense of smell)
• Constipation
• Depression and anxiety
• REM sleep behavior disorder (RBD) is a parasomnia characterized by the acting out of vivid dreams during the rapid eye movement (REM) phase of sleep. Individuals with RBD may vocalize, move, or even enact complex behaviors while dreaming, sometimes resulting in injury to themselves or their bed partners. This disorder is often seen in conjunction with neurodegenerative diseases such as Parkinson's disease. Early recognition of RBD can serve as a marker for potential development of such conditions, emphasizing its clinical significance as a prodromal symptom in those at risk.

Disease Course

• Parkinson's is incurable and progressive
• Leads to increasing disability
• Pharmacologic treatment aims to relieve motor symptoms
• Quality of life can be maintained for many years

Causative Factors

• Genetic Importance:
  • Critical in early-onset cases (under age 50)
  • Accounts for 10-15% of all cases
• Environmental Protective Factors:
  • Cigarette smoking
  • Coffee consumption
  • Anti-inflammatory drug use
  • High serum uric acid levels
• Environmental Risk Factors:
  • The teaching profession, which often involves standing for extended periods, managing large groups of students, and engaging in repetitive movements, may expose individuals to various physical stressors. This occupational exposure has been linked to a potential increased risk for developing Parkinson's Disease.
  • Healthcare work
  • Farming
  • Lead/manganese exposure
  • Vitamin D deficiency

Neurochemical Basis

• Dopamine Deficiency

  • Reduced dopamine in the basal ganglia
  • Loss of dopaminergic neurons in the substantia nigra
  • Disrupted inhibition of GABAergic cells in the corpus striatum

• Lower concentration of DA (dopamine) in the basal ganglia is reduced in Parkinson's

• Pharmacologic attempts restore dopaminergic activity which alleviate many motor symptoms of PD

• The complementary approach has been to restore the delicate balance of cholinergic and dopaminergic influences within the basal ganglia by utilizing antimuscarinic medications. These medications act to inhibit the action of acetylcholine, thereby helping to mitigate the effects of dopamine deficiency. By doing so, they aim to improve motor function and decrease the symptomatic burden of Parkinson's Disease. This strategy recognizes the complex interplay between neurotransmitters in regulating movement and behavior.

  Treatment Approaches

• Dopaminergic Enhancement through Levodopa or dopamine agonists

• Cholinergic Balance through Antimuscarinic drugs

• Targeting other neurotransmitters in Parkinson's Disease treatment involves understanding neurochemical interactions that affect motor control and behavior. While dopamine is the primary focus, variations in norepinephrine and serotonin also impact clinical symptoms. Norepinephrine depletion can worsen fatigue and other non-motor symptoms, raising questions about its therapeutic relevance compared to dopaminergic treatments. Further research is required to explore how enhancing norepinephrine could alleviate symptoms, ultimately improving patient outcomes and quality of life.

  • Norepinephrine depletion, clinical relevance is uncertain

Carbidopa/Levodopa

• Carbidopa and Levodopa are given together to treat Parkinson's Disease.

Levodopa Mechanism of Action

• Dopamine cannot cross the blood-brain barrier

• Levodopa (L-DOPA):

• Crosses blood-brain barrier via transporter

• Converted to dopamine in brain

• Acts on dopamine receptors

Dopamine Receptor Types

• D1 Family: D1, D5 receptors
  • Location: substantia nigra pars compacta
  • Presynaptic on striatal axons
• D2 Family: D2, D3, D4 receptors
  • Location: postsynaptic on striatal neurons
  • Primary target for therapeutic effects

Levodopa Pharmacokinetics

• Rapid absorption from the small intestine
• Affected by
  • Gastric emptying rate
  • Gastric pH
  • Food intake(delays absorption)
  • Competing amino acids
• Distribution & Metabolism
  • Peak plasma levels: 1-2 hours
  • Plasma half-life: 1-3 hours
  • Only 1-3% reaches brain unaltered
  • Main metabolites:
    • Homovanillic acid(HVA)
    • Dihydroxyphenylacetic acid(DOPAC)

Levodopa Clinical Use

• Strategy: Best results in first few years
• Often combined with carbidopa (decarboxylase inhibitor)
• Starting dose: Carbidopa 25mg + Levodopa l00mg (3x daily)
• Maintenance dose: Carbidopa 25mg + Levodopa 250mg (3- 4x daily)

Levodopa Adverse Effects

• Gastrointestinal (80% nausea and vomiting without carbidopa)
  • Nausea and vomiting
  • Anorexia
• Management strategies for gastrointestinal side effects include administering levodopa in divided doses throughout the day, taking it with meals to mitigate nausea, implementing a gradual increase in dosage, and adding carbidopa to enhance absorption and minimize side effects.
• Cardiovascular
  • Cardiac arrhythmias, postural hypotension, and possible hypertension
• Behavioral/Psychiatric
  • Depression, anxiety, confusion, hallucinations, and sleep disorders
• Management options for addressing behavioral and psychiatric adverse effects of levodopa include dose reduction, which can help alleviate symptoms, and the use of atypical antipsychotics, which may mitigate issues such as anxiety and hallucinations while minimizing potential side effects compared to traditional antipsychotics.

Levodopa Motor Complications

• Dyskinesias are involuntary movements from long-term levodopa treatment for Parkinson's disease, manifesting as chorea (jerky motions) and athetosis (slow movements), affecting around 80% of patients after ten years.

  Management of dyskinesias in Parkinson's disease includes adjusting levodopa dosage to minimize involuntary movements, using amantadine for some patients, and employing continuous delivery systems like infusion pumps. Early recognition and management of these motor complications are essential for preserving quality of life.

• Occurs in 80% after 10 years

• Dyskinesias in Parkinson's patients often manifest as choreoathetosis, which combines irregular, rapid movements with slower, twisting motions, highlighting the complexity of motor complications in treatment.

• Management:

  • Dose adjustment
  • Amantadine
  • Continuous delivery systems, like infusion pumps, offer a steady levodopa supply, reducing dosing fluctuations. This method enhances levodopa's pharmacokinetic profile, maintaining therapeutic levels and diminishing "on-off" effects that impair motor control. Such technology improves patient adherence and symptom management, ultimately enhancing the quality of life for Parkinson's disease patients.

Levodopa Response fluctuations

• The wearing-off effect occurs when levodopa's efficacy diminishes before the next dose, causing a return of Parkinson's symptoms like end-of-dose akinesia, stiffness, and slowness. Managing this involves adjusting dosages and timing, adding adjuvant medications, or using extended-release formulations for more consistent therapeutic coverage.
• The on-off phenomenon refers to the unpredictable fluctuations in motor performance experienced by patients taking levodopa for Parkinson's disease. During "on" periods, patients exhibit improved mobility and reduced symptoms, while "off" periods are marked by the emergence of stiffness, bradykinesia, and other debilitating Parkinson's symptoms. This phenomenon complicates disease management, as patients may face a rollercoaster of symptom control, necessitating careful medication timing and potential adjustments to their treatment regimen to minimize these fluctuations.
• Management: Dose adjustment, timing of protein meals, and extended-release formulations

Levodopa Contraindications

Absolute: Active psychosis( Active psychosis is a mental health condition characterized by disconnection from reality through delusions or hallucinations. It contraindicates levodopa use due to worsened psychiatric symptoms, necessitating stabilization before treatment.), MAO-A inhibitor use, and Angle-closure glaucoma

• Relative/Caution:Melanoma is a serious skin cancer originating from melanocytes, the cells that produce melanin. A history of melanoma influences treatment choices for Parkinson's disease, particularly regarding levodopa use due to risks of skin lesions or cancer exacerbation. Healthcare providers must assess and monitor skin conditions carefully before levodopa initiation.
• Cardiac disease,
• Peptic ulcer
• Open-angle glaucoma

Levodopa Drug Interactions

• Pyridoxine (vitamin B6)
• MAO inhibitors
• Protein-rich meals

Dopamine Receptor Agonists Advantages Over Levodopa

• Direct action on postsynaptic receptors
• No enzymatic conversion needed
• No toxic metabolites
• No competition for transport
• More selective receptor targeting

Clinical Applications

• First-Line Therapy: Lower incidence of response fluctuations and dyskinesias
• Limitations: The therapeutic effects of this medication are significantly less pronounced when compared to levodopa, which is the gold standard for treating Parkinson's disease. Additionally, patients may experience greater cognitive and emotional side effects, along with an increased likelihood of experiencing excessive sleepiness and fluid retention, known as edema.
• Combination Therapy: Added to Levodopa for; End-of-dose akinesia, On-off phenomenon, and Treatment resistance
• to mitigate side effects and enhance the overall efficacy of treatment regimens, improving patient outcomes and promoting better adherence to therapeutic protocols for Parkinson's disease management.

Pramipexole

• Newer Agents (Preferred)
• Mechanism of action involves a preference for D3 dopamine receptors, which play a crucial role in modulating motor control and reward pathways in the brain, offering advantages in effectiveness and reduced side effects in comparison to treatments targeting other receptor subtypes.
• Benefits: Effective as monotherapy, Helps in advanced disease and May improve affective symptoms
• Dosing: Start: 0.125mg TID, Maintenance: 0.5-1.5mg TID, and Extended-release available

Ropinirole

• The mechanism of ropinirole involves selective stimulation of D2 dopamine receptors, enhancing dopaminergic activity to alleviate Parkinson's disease symptoms, improving motor function and reducing motor fluctuations for patients.
• Dosing: Start: 0.25mg TID, Increase weekly, Maintenance: 2-8mg TID, Note: Metabolized by CYP1A2

Rotigotine

• Delivery: Transdermal patch
• Dosing: Start: 2mg/24h and Max: 6mg/24h
• Advantage: Continuous stimulation

Older Agents (Rarely Used)

• Bromocriptine
• Pergolide
  • Associated with valvular heart disease

Dopamine Agonists Adverse Effects

• Gastrointestinal - Nausea and vomiting, anorexia, constipation, dyspepsia, and peptic ulceration risk
• Cardiovascular - Postural hypotension, Digital vasospasm (ergot derivatives), Cardiac arrhythmias, Peripheral edema, and Valvulopathy (refers to a condition characterized by the dysfunction of one or more heart valves, which may lead to significant cardiovascular consequences.)
• Neurological/Psychiatric - Dyskinesias,
• Mental disturbances: Confusion, Hallucinations and Delusions
• Management: Atypical antipsychotics

Dopamine Agonists Impulse Control Disorders

• Prevalence: Up to 45%

• Manifestations: Compulsive gambling, Shopping, Sexual activity

• Risk Factors: Impulsive personality, History of addiction, Family history

• Management: Dose reduction, Medication withdrawal

• Withdrawal Syndrome

  • Symptoms
    • Physical: Hypotension, Nausea and Diaphoresis
    • Psychological: Anxiety, Panic attacks, Depression, Drug cravings

Dopamine Agonists Withdrawal Syndrome

• Management: Gradual tapering, Never stop abruptly and May need reintroduction
• Contraindications: Psychotic illness, Recent myocardial infarction, Active peptic ulceration, Peripheral vascular disease

Monoamine Oxidase Inhibitors

• Types of Monoamine Oxidase:
  • MAO-A Metabolizes: Norepinephrine, Serotonin, Dopamine.
  • MAO-B Selectively Metabolizes: Dopamine

Specific MAO-B Inhibitors

• Selegiline(Deprenyl)
  • Mechanism: Selective MAO-inhibitor at normal doses
    • Inhibits MAO-A at higher doses
  • Dosing:
    • 5 mg with breakfast
    • 5 mg with lunch
  • Clinical Use:
    • Adjunctive therapy involves additional treatments alongside primary therapy to enhance effectiveness in managing Parkinson's disease. It helps optimize treatment plans for individual patients, leading to improved control of both motor and non-motor symptoms. Common adjunctive therapies include medications, physical therapy, occupational therapy, and lifestyle changes.
    • For declining/fluctuating levodopa response
  • Benefits:
    • Enhances levodopa effect
    • Reduces levodopa dose requirement
    • May help with on-off phenomena
  • Side Effects:
    • Insomnia(if taken late in day)
• Rasagiline:
  • Properties:
    • More potent than selegiline
  • Uses:
    • Monotherapy in early disease
    • Adjunctive therapy in advanced disease
  • Dosing:
    • Monotherapy: 1mg/day
    • Adjunctive: 0.5-1 mg/day
  • Research:
    • ADAGIO trail Results:
      • 1 mg/day showed disease slowing potential
    • 2mg/day failed to show benefit
• Safinamide:
  • Primary Use:
    • Reduces response fluctuations
    • Not effective as monotherapy
  • Dosing
    • Start 50 mg daily
    • Maintenance : 100mg daily after 2 weeks

MAO-B Inhibitors Adverse Effects

• Enhanced effects of levodopa
• Dyskinesias
• Mental changes
• Nausea
• Sleep disorders
• Cardiovascular
  • May precipitate hypertension
  • May aggravate existing hypotension
  • Special Warning
  • Avoid combining levodopa with non-selective MAO Inhibiters
  • Risk of hypertensive crisis
  • Due to peripheral norepinephrine accumulation

MAO-B Inhibitors Clinical Considerations

• Benefits:

  • Extends levodopa effectiveness

  • May reduce motor fluctuations

  • Potential disease-modifying effects of therapies for Parkinson's disease are debated, with some studies indicating that medications affecting dopamine may manage symptoms and alter disease progression. However, evidence is inconsistent and requires further investigation for definitive conclusions.

  • Limitations

  • Minor therapeutic effect as monotherapy

• Variable evidence for disease modification
  • Need for careful medication management

Catechol-O-Methyltransferase (COMT) Inhibitors

• Mechanism of Action:
  • Inhibit peripheral levodopa metabolism
  • Decrease levodopa clearance
  • Increase levodopa bioavailability
  • Do not effect:
  • Time to peak concentration
  • Maximum concentration

Available COMT Inhibitors

• Entacapone:
  • Properties:
  • Peripheral effects only
  • Preferred agent
  • No hepatotoxicity
• Dosing: 200mg w/ each levodopa dose, Up to 6 times daily
• Half-life: ~2 hours
• Tolcapone:
  • Properties:
  • Central and peripheral
  • effects
  • More potent
  • Longer duration
• Dosing: 100 mg three times daily , May increase to 200 mg TID
• Limitations: risk of hepatotoxicity, requires liver monitoring
• Opicapone (Ongentys):
  • Properties:
    • Long-acting
  • Peripherally selective
  • Dosing: 50 mg once daily, Taken at bedtime

COMT Inhibitors Clinical Applications

• Help with response fluctuations
• Provides
  • Smoother response
  • Longer on-time
  • Reduced total levodopa needs
  • Not beneficial:
• As monotherapy
  • With initial levodopa therapy

COMT Adverse Effects

• Dopaminergic Effects
  • Dyskinesias
• Nausea
  • Confusion Often requires 30% levodopa dose reduction
• Other Side Effects
• Diarrhea Abdominal pain
• Orthostatic hypotention
• Sleep disturbances
• Orange urine discoloration
• Tolcapone-Specific:
• Liver enzyme elevation and risk of acute hepatic failure

Combination Product

• Components: Levodopa plus Carbidopa plus Entacapone
• Benefits: Simplified regimen, fewer tablets, and greater symptomatic benefit
• Considerations: Earlier dyskinesia onset, increased dyskinesia frequency, and no increased cardiovascular risk

Apomorphine

• Potent nonergoline dopamine agonist Acts on D2 receptors
• Clinical Use:
• Rescue Therapy:
• For "off-periods" of akinesia
• Rapid onset (10 minutes)
• Duration: up to 2 hours
• Dosing: Range 0.3-06 mL (3-6 mg), Maximum 5 times daily, Can be given as continuous infusion
• Side effects: Nausea (requires antiemetic pretreatment), Dyskinesias, Drowsiness/insomnia, Hypotension/syncope, Injection site reactions, Behavioral disturbances

Amantadine

• Antiviral agent with antiparkinsonian effects

  Possible mechanisms

• Potentiates dopaminergic function Antagonizes adenosine A2A receptors

• NMDA receptor antagonist Clinical Benefits

• Reduces bradykinesia, rigidity, tremor

• May alleviate movement disorders caused by medical treatment side effects.

• Benefits may be short-lived

  Adverse Effects

• CNS effects

  • Restlessness
  • Depression

• Hallucinations

• Confusion

• Physical effects

• Livedo reticularis is a skin condition marked by a mottled, purplish discoloration resembling a net-like pattern, caused by changes in small blood vessel blood flow. It can stem from vascular disorders, autoimmune diseases, and medications. Symptoms may include cold sensitivity and discomfort, potentially indicating underlying systemic issues that need evaluation.

  • Peripheral edema
  • Gastrointestinal disturbances

Istradefylline

• Caffeine analog
• Adenosine A2A receptor antagonist
• Usage
  • Dosing: 20.40 mg daily
  • Reduces off-periods
  • Improves motor function
• Side effects
  • Dyskinesias Dizziness
• Psychiatric symptoms
• Sleep disturbances

Drug Treatment Summary

• Gut Levodopa (1)
• Peripheral Tissues 3-O-Methyldopa, Entacapone (3), Levodopa, Carbidopa (2), and Dopamine (1)
• Brain 3-O-Methyldopa, Entacapone (3), Striatal neuron, Levodopa, Dopamine, Amantadine Increases, Dopamine, Selegiline (4), Dihydroxyphenylacetic acid (DOPAC) + H2O2.
• Bromocriptine (D1 and D2 receptors)

Surgical Procedures

• Deep Brain Stimulation Benefits
• Manages clinical fluctuations
• Contro15 dyskinesias
• Reduces medication needs
• Contraindications:

Secondary parkinsonism refers to a form of parkinsonism that results from external factors rather than being a primary neurodegenerative condition like Parkinson's disease. These external factors can include a variety of medical conditions, certain medications, toxins, and head trauma. In contrast to primary Parkinson's disease, secondary parkinsonism can often reverse or improve when the underlying cause is addressed.

       Dementia

• Poor response to dopaminergic drug
• Other Procedures
• Focused ultrasound thalamotomy
• Cellular transplantation (investigational) Neuroprotective Therapy Investigated agents (Not Proven Effective) Antigenic
• Antiapoptotic agents
• Glutamate antagonists
• Neurophilic factors
  • Anti-inflammatory Drug
• Current Research
• Deferiprone Exenatide
  • α-synuclein immunization
• Biomarker development

Gene Therapy Trials

• Glutamic acid decarboxylase 2.Arpmatic add decarboxylase (ADC)

3. Newtutin -3. Prosavin (Three-Gene Approach) -Current Status Phase 1/2 trials completed Some encouraging results -Requires further rescarch

Non-Motor Symptom Management

• Cognitive Decline:
• Rivastigmine: 1.5-6 mg BID
• Memantine: 5-10 mg daily Donepezil: 5-10 mg daily
• Other Manifestations Depression/anxiety: antidepressants Psychosis: atypical antipsychotics
• Sleepiness: modafinil
• Autonomic symptoms: targeted therapy

Treatment Strategy Overview

• Early Disease:
  • Aviod premature treatment
  • Consider
  • Rasagiline
  • Selegiline
  • Amantadine
  • Antimuscarinics (Young Patients)
• Advanced Disease: Carbidopa-levodopa
• Dopamine Agonist
• COMIT inhibitors
• Deep brain stimulation
• Physical therapy

Other Movement Disorders

• Physiologic Tremor: Enhanced by anxiety fatigue, thyrotoxicosis, epinephrine/isoproterenol.
• Drug-induced enhancement: bronchodilators, valproate, tricyclic antidepressants, lithium
• Essential Tremor:
• Characteristics: Postural tremor, Sometimes familial (Autosomal Dominant) affect hands, head, voice,legs.
• Treatment
• • Propranolol: 120-320 mg/day.
• Metoprolol if pulmornary contraindications).
• Gabe-enhancing Drugs
• -Primidone up to 250mg TID
• Gabapentin: 100-2400mgday
• Other options Alprazilam up to 3mg daily Botulinum Foxin injections Thalamus stimulation surgery

Huntington disease

Pathophysiology

• Autosomal dominant inheritance
• CAG trinucleotide repeat expansion involves the repetition of cytosine, adenine, and guanine nucleotides in specific genes, notably linked to neurodegenerative disorders like Huntington's disease. This expansion in the HTT gene produces a mutated huntingtin protein, causing neuronal dysfunction. The length of the CAG repeat correlates with symptom severity and onset, illustrating genetic instability risks in hereditary diseases.
• Imbalance of neurotransmitters Dopanine
• Acetylcho line Gabo Treatment
• -Dopamine Antagonism1 Tetrabenazine: 125-50 mg TID
• Phenothiazines Haloperidol: Stert img BID
  -Fluphenazine Clonazapire: 10-30 mg daily Fewer Agents Deutetramenazine: + mg daily
• Support Services Genetic counselling Speech thereph
• Physical/occupational therapy
• Dysphasia Management Huntington disease:
• Pathophysiologys of Huntington’s is a background information

Tics are involuntary, repetitive movements or sounds, ranging from simple (e.g., blinking, head jerking) to complex tics involving coordinated actions or vocalizations. Tourette Syndrome (TS) is a neurological disorder featuring multiple motor and vocal tics, typically starting in childhood due to genetic and environmental factors. Symptoms can vary in severity, often worsening with stress. Management includes behavioral therapies like Habit Reversal Training and, in some cases, medications to reduce tics. TS may co-occur with disorders such as ADHD and OCD, necessitating comprehensive treatment. Early diagnosis improves the quality of life.

• Education:
  • Behavioral interventions
• a2- adrenergic agonists
• Cloning: A biotechnological process used to create a genetically identical copy of an organism or cell, facilitating advances in genetics and medicine.
• Guanfacine New Treatments
  • Ecopipam Balinum latin focal tics Depp brain stimulation

Dyskinesia

Treatment; Benzhoprine, Dipenhydromine Biperiden, Diazepam

Restless Legs Syndrome

• Treat Underlying Caused Iron deficiency Medication riviww

  • Lifestyle modifications.

• Pharmacology

• Gabepantir , Pregabalin, Clonazepam, oats when Recessary

Wilson Disease

• Copper metabolism disorder
• ATP7b gene mutations clinical features: Hepatic disfunction Neurologic symptoms, Psychiatric symptoms Kayser- Fleischner rings Treatment capper Removal Benyopine Diperdin Diazopain copper absorption prevertion, Zinc acetate

Azheimers disease

• AD Is A progressive type of dementia for which no cause is known and not care has been found
• AD results from the destruction of cholinergic and other newons on the cortex and limbic structures of the brain particularly the amygdala basal forebion and hippocamps
• Treatment Incl central ace-I
• Donepizil Memanties