Lecture Notes on Neurological Disorders

Alterations in Neurotransmission - Pathophysiology

Cerebral Palsy (CP)

• Definition: "Brain condition causing paralysis"
• Impact: Damages thoughts, movements, and causes loss of muscle control.
• Effects: Can affect vital organs.
• Description: A group of disorders affecting muscle movement and coordination due to brain damage occurring before, during, or after birth.
• Prevalence: Most common motor childhood disability.
• Symptoms: Affects muscle tone, movement, and posture.
• Progression: Symptoms change over time as the child grows, but it is not considered a progressive disease.
• Cure: No cure.

Etiology/Causes of CP

• Congenital CP:
  • Occurs before or during birth (85-90% of cases).
  • Factors: genetics, brain malformations, infections during pregnancy, strokes, or injuries to the developing brain.
• Acquired CP:
  • Occurs after birth and is less common.
  • Caused by brain damage from infections, such as meningitis and encephalitis.
• Other Conditions:
  • Stroke or brain injury that limits blood flow to brain tissue.
  • Traumatic injury.

Types of CP

• Spastic CP:
  • Most common.
  • Stiff, tight muscles and exaggerated reflexes.
• Dyskinetic CP:
  • Uncontrollable movements.
  • Difficulty controlling extremities, hands, and feet.
• Ataxic CP:
  • Affects balance and coordination, leading to unsteadiness.
• Mixed CP:
  • Symptoms of more than one type.

Signs & Symptoms of CP

• Abnormal muscle tone (spasticity or hypertonia).
• Motor skills delay.
• Balance and posture issues.
• Speech and swallowing issues.
• Sensory impairments.
• Seizures.
• Learning disabilities.
• Others: drooling, difficulty with fine motor movements, pain, bowel and bladder issues.

Signs of CP Before Diagnosis

• 0-3 Months: Poor reflexes and muscle control.
• 3-6 Months: Poor muscle development and communication.
• 6 Months - 1 Year: Trouble with fine, gross, and oral motor skills, lack of familiarity, poor coordination.
• 1-2 Years: Awkward muscle tone, delayed physical, cognitive, social, and/or emotional development.

Symptoms of CP

• Abnormal Tone
• Abnormal Strength
• Abnormal Reflexes
• Loss of Control or Coordination
• Persistent Motor Delay
• Posture or Balance Problems
• Associated handicaps
• Cognitive Deficit

Example: "Scissor Gait"

Diagnostic Testing and Treatment of CP

• Nature: Life-long condition.
• Cure: No cure.
• Diagnosis: Usually diagnosed in infancy or early childhood.
• Tests: Developmental screening tests, physical presentations and deficits, CT scans, MRI, genetic and metabolic testing.
• Treatments: Focus on preventing physical deformities, improving mobility, and maximizing independence. Physical therapy, occupational therapy, medications (antispasmodics, seizure medications, etc.), assistive devices, and surgeries.

CP - Healthcare Team

• Pediatrician
• Neurologist
• Nurse
• Speech-language pathologist
• Occupational therapist
• Gastroenterologist
• Dietitian
• Social Worker

Multiple Sclerosis (MS)

• Q > (3:1) - (gender ratio)
• Age of onset: 20-40 years.
• Increased prevalence in regions further from the equator.
• Pathophysiology: Autoimmune inflammation, demyelination, and axonal degeneration of the CNS.

General Symptoms

• Visual and cranial nerve dysfunction.
• Headache.
• Fatigue.
• Pain.
• Internuclear ophthalmoplegia.
• Autonomic symptoms.
• Bowel, bladder, and sexual dysfunction.
• Optic neuritis.
• Trigeminal neuralgia.
• Sensory disturbances: Paresthesia

Diagnostics

• McDonald criteria: dissemination of CNS lesions in time and space.
• MRI: multiple demyelinated sclerotic plaques in periventricular white matter.
• Lumbar puncture: oligoclonal bands and lymphocytic pleocytosis.

Management

• Exacerbations: high-dose glucocorticoids, plasmapheresis, ACTH gel.
• Long-term: disease-modifying therapy (e.g., interferon therapy, monoclonal antibodies), symptom management, supportive care.
• Uhthoff phenomenon: Temporary symptom exacerbation at body temperature.
• Lhermitte sign
• Motor dysfunction: Muscle weakness, spasticity, hyperreflexia
• Impaired gait

MS - Nerve Damage

• Normal Nerve: Intact myelin sheath.
• MS Nerve: Damaged myelin sheath.

MS Types and Treatments

• Clinically Isolated Syndrome (CIS):
  • One symptomatic episode (mono- or multifocal) lasting at least 24 hours.
  • Treatment: Disease-modifying therapy recommended (see RRMS).
• Relapsing-Remitting MS (RRMS):
  • Relapses of disease activity followed by remissions (when symptoms are mild or absent).
  • Treatment: Disease-modifying therapy (including interferon beta-1a, interferon beta-1b, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, and ocrelizumab). Corticosteroids (including methylprednisolone, prednisone).
• Primary-Progressive MS (PPMS):
  • Progressive worsening of neurological functioning (with short periods of stability) from onset of symptoms.
  • Treatment: Disease-modifying therapies more recent, including rituximab and ocrelizumab.
• Secondary-Progressive MS (SPMS):
  • When RRMS transitions into the progressive form of worsening of neurological functioning.
  • Treatment: One disease-modifying therapy available (i.e., mitoxantrone).

Main Symptoms of MS

• Central: Fatigue, cognitive impairment, depression, anxiety, unstable mood.
• Visual: Nystagmus, optic neuritis, diplopia.
• Speech: Dysarthria, Dysphagia
• Musculoskeletal: Weakness, spasms, ataxia
• Sensation: Pain, hypoesthesias, paraesthesias
• Bowel: Incontinence, diarrhea or constipation.
• Urinary: Incontinence, frequency or retention.

MS Goals of Treatment

• No cure for MS.
• Goals of treatment are to manage symptoms, slow progression of the disease, improve quality of life and independence.

Common Disease Modifying Drug Types for MS

• Novantrone (mitoxantrone)
• Ocrevus (ocrelizumab)
• Tysabri (natalizumab)
• Lemtrada (alemtuzumab)

Hydrocephalus (HC)

• Pathophysiology: Too much cerebral spinal fluid (CSF) accumulates in the brain’s ventricles.
• Causes the ventricles to widen and swell, increasing pressure in the skull, which can damage brain tissue and affect brain function.
• Types: Can be congenital (at birth) or acquired (develops later in life).
  • Congenital: Genetic, neural tube defects (spina bifida), infections during pregnancy (rubella), Aqueductal stenosis (narrowing of the brain ventricle passage).
  • Acquired: Head trauma, stroke, tumors, infection, and bleeding.

Signs & Symptoms of HC

• (Newborns, Infants, Children): Rapid increase in head circumference and size, unusually large head, bulging and/or tense fontanels (“soft spots”), vomiting, lethargy, sleepiness, irritability, eyes fixed downward (“Sun setting gaze”), seizures, problems with muscle tone, poor feeding.
• (Older children and adults): Headache, vomiting, visual changes, balance and coordination problems, memory and concentration difficulties, loss of bladder control, fatigue, lethargy, and sleepiness, personality changes, delays in developmental milestones, difficulty walking "shuffling", tremors.

Treatment of HC

• Ventriculoperitoneal (VP) Shunts: Ventricles, Ventricular Catheter, Valve

Parkinson's Disease (PD)

PD Statistics and Prevalence in the USA:

• Approximately 1 million people in the US have PD.
• 1 out of every 336 people.
• The rate of individuals diagnosed is increasing.

Risk factors:

• Age (65+ years and older).
• Sex (occurs more in men than women).

Parkinson’s disease:

• Progressive neurodegenerative disorder that affects movement.
• Loss of nerve cells that produce dopamine (chemical messenger) necessary for smooth and coordinated movement.
• Deficiency of dopamine leads to decline and loss of motor movements.

Causes of PD:

• Idiopathic
• Genetics (10-15% have a family history)
• Environmental exposures to pesticides and other chemicals
• Lewy Bodies: The abnormal “clumping” of proteins called \alpha-synuclein in the brain.

Parkinson's Disease - Motor and Non-Motor Impairments

• Motor impairments
  • Bradikinesia
  • Postural imbalance
  • Tremor
  • Muscular rigidity
  • Walking difficulties
  • Freezing of movements
• Non-motor impairments
  • Cognitive impairment
  • Hypersalivation
  • Sleeping disorders
  • Mood disturbances
  • Gastrointestinal issues
  • Sweat and olfatory disorders
  • Anxiety and depression
  • Pain

Parkinson's Disease Symptoms

• Stooped posture
• Masked Face
• Back rigidity
• Forward tilt of trunk
• Flexed elbows and wrists
• Hand tremor
• Tremors in the legs
• Slightly flexed hip and knees
• Shuffling, short-stepped gait

Diagnosis and Treatments:

• There are no definitive tests that diagnosis non-genetic PD.
• Mainly diagnosed from the patient’s medical history and symptoms.
• Response to Levodopa can help confirm diagnosis.
• Brain imaging to rule out other diseases and conditions that may be causing symptoms.

Treatments:

• No cure, but the goal is to manage symptoms and maintain quality of life.
• Medications:
  • Levodopa: Replenishes dopamine levels in the brain (considered the most effective treatment).
  • Dopamine Agonist: Mimics dopamine effects in the brain.
  • Enzyme inhibitors: Prevents the breakdown of dopamine in the brain.
• Other treatments and supportive measures:
  • Physical therapy
  • Exercise
  • Diet
  • Surgeries