Clinmed2test3: Neurodegenerative and Demyelinating Disease ppt:

Multiple Sclerosis (MS)

Burden on Patients with MS (PwMS)

• Wide range of symptoms, including loss of vision, ataxia, tremor, bowel incontinence, urinary incontinence, generalized pain, fatigue, memory and learning problems, depression, and anxiety
• Initial symptoms often appear between 20 and 40 years of age

Pathophysiology

• Etiology: Unknown
• Pathogenesis: Central Nervous System (CNS) immune-mediated inflammation and demyelination, along with axonal degeneration

Risk Factors

• Genetic: Family History, Specific Genes (HLA-DRB1), Caucasian, Female
• Environmental: Ambient UV Radiation, Dietary (Vitamin D), Infectious (EBV), Tobacco Use

Types of MS

• Relapsing (RRMS)
  • Most common type
  • Characterized by relapses (symptoms getting worse) followed by recovery (remission)
  • Disability doesn't worsen between relapses, but can worsen after each relapse
• Secondary Progressive (SPMS)
  • Have increasing disability, but no relapses
  • Typically occurs 15-20 years after diagnosis
• Primary Progressive (PPMS)
  • Neurologic functions worsen steadily from the beginning
  • No symptom flare-ups (relapses) and no recovery (remission)

Prognosis

• Relapsing course is generally associated with a better prognosis than a progressive course
• High lesion load on MRI early in the disease is associated with greater long-term disability
• Psychosocial stress has been linked to an increased risk of relapse and pseudo-relapse

Clinical Features

• History: Single episode or multiple episodes of neurological impairment, separated by a period of time with less or no symptoms
• Neurocognitive: Cognitive impairment
• Motor - Somatic: Spasticity, Weakness, Tremor
• Motor - Autonomic: Sexual Dysfunction, Overactive Bladder, Underactive Bladder
• Sensory: Visual Impairment, Trigeminal Neuralgia, Sensory Disturbance
• Other: Fatigue, Seizure, Lhermitte's Sign, Uhthoff Phenomenon

Relapse, Remission, & Pseudo-Relapse

• Pseudo-Relapse: Caused by infectious, metabolic, physiologic stress, or psychosocial stress
• Relapse: Characterized by new symptoms or worsening of existing symptoms
• Remission: Symptom improvement or recovery

Optic Neuritis

• One of the initial MS events
• Pathogenesis: Inflammatory demyelination of the optic nerve
• Clinical Features: Painful, monocular visual loss, often with papillitis
• Long-term: Relative afferent pupillary defect, color desaturation, optic atrophy
• Diagnostic Studies: Ophthalmologic examination, MRI brain and optic nerves
• Management: High dose steroids
• Prognosis: MS presenting symptom in 15-20% of patients, often with complete visual improvement

Transverse Myelitis

• General: Idiopathic, often post-infectious
• Secondary to multiple sclerosis, neuromyelitis optica, and acute disseminated encephalomyelitis
• Pathogenesis: Inflammatory demyelination of the spinal cord
• Clinical Features: Rapid onset, weakness, sensory alterations, and bowel/bladder dysfunction
• Diagnostic Studies: MRI brain and spine, CSF for markers of secondary causes
• Management: High dose steroids
• Prognosis: MS presenting symptom in 5-10% of patients, often with partial recovery

Diagnostic Studies

• Magnetic Resonance Imaging (MRI): MS most commonly involves cerebral hemispheres, periventricular regions
• Cerebrospinal Fluid Analysis:
  • Description: Clear, Colorless
  • Cell Count: Usually < 5/mm3, Rarely > 50/mm3
  • Protein: Normal or slightly elevated (rarely > 100/dL)
  • Glucose: Normal
  • IgG Index: Elevated
  • Oligoclonal IgG Bands >4
• Optic Coherence Testing: Measures retinal nerve thickness, used in patient with recurrent optic neuritis and normal MRI, or differentiating NMSOD from MS

Management

• Relapsing:
  • Acute Inflammation: High dose corticosteroids
  • Disease-Modifying Therapy: Immunomodulation or immunosuppression
  • Associated Neurological Symptoms: Treatments vary
• Progressive:
  • Acute Inflammation: High dose corticosteroids
  • Disease-Modifying Therapy: Immunomodulation or immunosuppression
  • Associated Neurological Symptoms: Treatments vary
• No cure, but the disease is manageable with lifelong treatment
• Continuous decision-making process for treatment, considering patient preferences, efficacy, safety profile, side effects, route of administration, and cost

Gullain-Barré Syndrome

• Most common cause of acute flaccid paralysis in healthy infants and children
• Neuromuscular emergency
• Pathophysiology: immune-mediated demyelination or axon injury leading to dysfunction of peripheral nerves
• Potential antecedents: infection, immunization, surgery, trauma, bone marrow transplant, and systemic disorders
• Clinical features: 4 phases, progressive, mostly symmetric, motor > sensory impairment, distal to proximal
• Evaluation: Brighton criteria, NCS, CSF, MRI neuroaxis, and M-F variant
• Management: inpatient, plasmapheresis, intravenous immunoglobulin, mechanical ventilation assistance
• Prognosis: most experience continued progression for up to two weeks, followed by a plateau phase, and then gradual recovery

Myasthenia Gravis

• Bimodal onset: 30 and 50
• Pathophysiology: autoimmune destruction of acetylcholine receptors on the surface of skeletal muscles
• Clinical features: insidious onset, fluctuating, muscle weakness, fatigability, axial and limb muscles, cranial nerves, and respiration
• Symptoms improve with rest
• Ocular type: ptosis, EOM weakness
• Lambert-Eaton type: proximal weakness, can be associated with cancer
• Evaluation: antibody testing, serum AChR antibodies, ice pack test, and CT or MRI of chest for thymoma
• Management: cholinesterase inhibition, pyridostigmine, immunotherapy, prednisone, and IVIG or plasmapheresis
• Prognosis: maximal extent at 3 years in majority of patients, course may be progressive or relapsing-remitting

Amyotrophic Lateral Sclerosis (ALS)

• Average onset: 56-63 years
• Pathophysiology: neurodegenerative, protein accumulation, oxidative stress, inflammation, death of upper and lower motor neurons
• Genetic factors, including mutations, sporadic (90%)
• Clinical features: upper limb, lower limb, bulbar, cognitive changes, no sensory symptoms, upper motor neuron and lower motor neuron findings
• Upper motor neuron findings: increased muscle tone, spasticity, hyperactive deep tendon reflexes, pathologic reflexes
• Lower motor neuron findings: decreased muscle tone, muscle atrophy, fasciculations, reduced or absent deep tendon reflexes
• Pseudobulbar affect: episodic, sudden uncontrollable and inappropriate laughing or crying
• Evaluation: upper and lower motor neuron signs in 3 regions, electromyography, denervation, genetic testing
• Management: goals of care, slow disease progression, maintain function, safety, comfort, two types of therapies (disease modifying and symptomatic)
• Disease modifying therapies: riluzole, oral therapy, prolongs survival by an average of 2 months, may improve quality of life