Neuro Disorders- Parkinsons, CP, MS

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Parkinsons Disease Stats

Degenerative Diseases Parkinson Disease
Occurs after age 40
Mean onset 58 - 62 years
Males have a higher incidence
Primary CNS disorder
Leading cause of neurological disability in people 60 years or older
500,000 affected in the US

History of Parkinsons

Degenerative Diseases Parkinson Disease
James Parkinson, 1755-1824
Produces abnormal movement
Disorder of the basal ganglia
Alteration in the dopamine-secreting "nigrostriatal pathway"
Loss of dopamine-secreting neurons(they die)

Possible Causes of Parkinsons

Degenerative Diseases Parkinson Disease
Parkinson's 10 - 15% inherited
Secondary Parkinson disease - Caused by other factors
Toxins
Drugs - recreational drugs (MPPP)
A synthetic opioid drug MPPP when produced can have MTPT as an impurity(self induced parkinsons)
MPTP causes degeneration of the substantia nigra region

Secondary Parkinson disease - Caused by other factors
Virus (influenza) after world war II (1920s)
Influenza pandemic - increases in PD
Contact with large numbers of people
Free radicals
PD patients appear to have enhance free radical levels

Age may predispose substantia nigra region increase sensitivity to damage(older higher incidence of parkinsons)
Toxins have been implicated

Major disease feature of parkinsons

Degenerative Diseases Parkinson Disease
Major disease feature
Degeneration of dopaminergic nigrostriatal pathway
Damage in neurons remaining in the substantia nigra appears as
Intracytoplasmic eosinophilic inclusions
Lewy body (round bodies found in vacuoles)

Loss of dopamine receptors (D1) in the basal ganglia
Severity of the disease depends on the number of neurons damaged in the substantia nigra

Pathophys of Parkinsons

Degenerative Diseases Parkinson Disease
Pathophysiology
Loss of dopamine (NT) - inhibitory function
Imbalance between excitatory and inhibitory NTs
Excessive acetylcholine (excitatory NT) because of a loss of inhibition(dopamine)
Resulting in
Hypertonia (tremor and rigidity)
Akinesia (temp loss of muscle movement)
Bradykinesia (slow movement)

Parkinson's Symptoms

Degenerative Diseases Parkinson Disease
Pathophysiology
Symptoms appear after 60 - 90% of dopamine secreting neurons are damage at the nigra region
Symptoms (classic) - all are present
Tremor
Rigidity (muscle stiffness)
Akinesia (poor movement)
Postural abnormalities

Parkinson's Tremor

Tremor
Asymmetric, regular and rhythmic tremor(one sided)
Late phase of the disease
tremor increases in frequency and amplitude

Parkinson's- Postural abnormalities

Postural abnormalities
Due to loss of postural reflexes
Postural fixation - unable to maintain upright position
Equilibrium problems
Disorders in righting (correcting posture)

Parkinson's-neuroendocrine aspect

Neuroendocrine
Basal ganglia influences hypothalamus
Activation of the hypothalamus - pituitary pathway
Results in excessive androgen secretion
Sebum secretion - oily skin
Cognitive symptoms
Endogenous depression (due to pathological factors)

Parkinson's Treatment

L - dopa (levodopa) - precursor to dopamine
Dopamine is too large to cross the blood brain barrier
Anticholinergic drugs
inhibit acetylcholine(suppresses excitation)
Substantial side effects from these drugs and are used during later stages of the disease
Fetal cell implants (dopamine secreting neurons)- improve but do not last long
Stem cells may also be useful- may make dopamine receptors and inject into brain

Surgical Treatments-parkinsons

Previous surgical methods destruction of pathways to reduce tremor
Pallidotomy- globus pallidus- has bad side effects
Thalamotomy-thalamus
Deep Brain Stimulation (DBS)
No destruction of brain regions

Deep Brain Stimulation

Impulse generator
Electrode surgically implanted
Generator implanted under the skin
Patient can actived/deactivated
External magnet
If tremor gets worse can activate it
Current disrupts the excitation and inhibition imbalance


Electrode delivers small current
Blocks disruptive signals causing tremor
Adjust current to optimize suppression of tremor

Multiple Sclerosis- Stats

Degenerative Diseases Multiple Scelerosis (MS)
Onset 20 - 50 years (peaks age 30)
Male/female ratio (1:2)
Leading neurologic disability in younger adults

Major abnormal physiology
Demyelination of CNS neurons

Optic Symptoms-MS

Degenerative Diseases Multiple Scelerosis (MS)
Symptoms - mixed (general) type
Optic neuritis (optic nerve demyelination)
Impaired central vision
Blurring, fogginess, haziness
Impaired color vision
Regions of diminished vision
Defective pupillary reaction

NS Symptoms-MS

Degenerative Diseases Multiple Scelerosis (MS)
Symptoms - mixed (general) type
Brain stem related symptoms
Internuclear ophthalmoplegia
Lateral gaze paralysis
Spinal involvement
Cerebellar involvement- involved in movement and memory of movement

Pathophys-MS

Degenerative Diseases Multiple Scelerosis (MS)
Pathophysiology
Suggested viral infection (immune challenge) or stress (pregnancy) occurs in patients that are genetically predisposed to MS
Resulting in an abnormal immune response in the CNS
T-lympocytes produce antibodies to a single myelin membrane protein
Patients have elevated IgG in CSF- have crossed the blood brain barrier for some reason and caused damage in the NS

Sequence of Events- MS

Degenerative Diseases Multiple Scelerosis (MS)
Pathophysiology (continued)
Demyelination process and nerve fiber loss due to axonal break
Sequence of events of MS
Interaction between the systemic immune system and the CNS (autoantibodies)
Demyelinating lesions (plaques occur)- antibodies attack patients own myelin

Molecular Level Pathophys-MS

Immune cells damage the myelin sheath
Glutamate is released
Glutamate binds to receptors on the oligodendrocytes
"Oligos" - glial cells producing myelin in the CNS
Glutamate accumulates within the glial cells
Excessive excitation of the cells- leads to cell stress, damage, or death
Communication along the neuron is gone

Treatment

Directed at acute management and reducing relapse frequency
Steroid hormones - adrenocorticotropic steroids
Suppress the immune responses
"Copaxone"(glatiramer acetate)
"decoy" protein analog of myelin
Autoantibodies bind to decoy protein and protect myelin
NEW TREATMENT- Betaseron

Betaseron

Betaseron = synthetic interferon 1b
Reduces relapse and severity
Less damage to neuronal tracks
Side effects- flu-like symptoms

Betaseron Mechanism

Betaseron = Interferon (IFNs) = cytokines
Activates immune system-inhibits viral infections and is ant-iinflammatory
Inhibits blood brain barrier leakage-prevents leakage of antibodies into the brain
Suppresses anti-myelin T-cells(suppresses cells that make autoantibodies that cause myelin destruction)
Some antigens stimulate release of IFNs(interferons)

Cerebral Palsy- stats

800,000 adults/children in the US
10,000 babies develop CP in the US
Treatments/prevention have not improved these numbers (30 years)

Symptoms- CP

General Symptoms (children)
Ataxia = lack of muscle coordination
Spasticity = stiff/tight muscles
Variations in muscle tone
Hypertonia- stiff/rigid
Hypotonia- relaxed or limp
Difficulties in swallowing/speaking/drooling
Tremor or random involuntary movement
Difficulties in precise movements (eg. writing)

RIsk Factors for CP

Low birth weight and premature birth
multiple births
Infections during pregnancy
Blood type incompatibility
Toxic substances
Maternal thyroid abnormalities or seizures
Breech birth
Complicated labor/delivery
Low apgar score (assess fetal development)
Jaundice- high fetal bilirubin levels
Highly neurotoxic
Seizure

4 Types of Damage to brain- CP

Four types of brain damage cause symptoms
Periventricular leukomalacia- damage to white matter or neuronal tracts of the brain
Cerebral dysgenesis- abnormal congenital development of brain
Intracranial hemorrhage- intracranial bleeding
Hypoxic-ischemic encephalopathy- lack of oxygen

paraventricular leukomalacia

Periventricular leukomalacia
White matter - CNS signal transmission pathways disrupted
During development damage can occur
Maternal or fetal infection
Injury during development- trauma or drugs

cerebral dysgenesis

Cerebral dysgenesis
Factors interfering in fetal development
Mutation in genes regulating development
Infections
Fevers
Traumas

Intracranial hemorrhage

Intracranial hemorrhage
Factors leading to fetal stroke
Blocked or damaged blood vessels
Maternal hypertension
Materanl pelvic inflammatory disease

Hypoxic Ischemic encephalopathy

Hypoxic-ischemic encephalopathy
Factors reducing oxygen
Interruption in breathing (parturition)
Low maternal BP
Rupture of uterus
Detachment of placenta
Umbilical cord problems

Diagnosis of CP

Diagnosis - imaging identify damage
Cranial ultrasound
Computed tomography (CT) scan
Magnetic resonance imagin (MRI)

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