Huntington’s Disease Progressive autosomal dominant neurodegenerative disorder caused by expansion of a CAG (cytosine ,adenine , guanine ) repeat coding for polyglutamine in the huntingtin protein. Genetics Review • Chromosomes - are located in the nucleus • They provide the instructions for all the information necessary for the living organism to grow and function • These instructions come in form of a complex molecule called DNA (Deoxyribonucleic Acid). DNA- Blueprint of life • DNA comes in compact form, a twisted ladder shaped molecule called a double helix. • Composed of a string of nucleotides. The 4 units are adenine (A), thymine (T), cytosine (C), and guanine (G). Genes • “Functional” regions of DNA that contain specific instructions are called genes. • Example would be regions of DNA that code for making proteins. Huntingtin Protein • Cytoplasmic protein found in almost all tissues of the body and brain • Normal function is not well understood, yet implicated in cell membrane recycling and neuroprotection. • Studies suggest that huntingtin protein regularly interacts with other proteins found in the brain • The altered form of huntingtin protein leads to nerve cell death in brain. Genetic Mechanism of HD: Unstable Trinucleotide repeat • The gene responsible for causing HD is located in chromosome 4. The gene regulates the production of huntingtin protein. • Huntingtin protein contains within it the amino acid glutamine (C-A-G). In people with HD, however, there is an excess number of glutamine. • That is why HD is often referred to as a trinucleotide repeat disorder HD = Huntingtin protein with expanded CAG (glutamine) tract CAG repeat 10 – 35 in normal individuals More than 40 repeats in diseased patients Proteins must be folded normally to function. Mutant expansion of CAG causes an unusual huntingtin protein which clumps together in the cell and causes neuronal cell death (in the brain only) How much CAG expansion is too much? • People with 10 to about 35 copies of CAG have a normal functioning form of the huntingtin protein. • Expansion of 40 or more CAG repeats is often full penetrance and the person will develop HD. • For people who have 36 to 39 copies of CAG, the outcome is less clear. Some will develop the symptoms of Huntington's disease and some will not. Neuropathology of HD • HD involve atrophy and cell death of the basal ganglia, the complex subcortical structures involved in control of motor movement, cognition and sensory pathways. • Specifically, there is a progressive and marked degeneration of the caudate and putamen (striatum).
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Huntington’s DiseaseProgressive autosomal dominant neurodegenerative disorder caused by expansion of a CAG (cytosine ,adenine , guanine ) repeat coding for polyglutamine in the huntingtin protein.
Genetics Review• Chromosomes - are located in the nucleus• They provide the instructions for all the
information necessary for the living organism to grow and function
• These instructions come in form of a complex molecule called DNA (Deoxyribonucleic Acid).
DNA- Blueprint of life• DNA comes in compact form, a twisted
ladder shaped molecule called a double helix.
• Composed of a string of nucleotides. The 4 units are adenine (A), thymine (T), cytosine (C), and guanine (G).
Genes• “Functional” regions of DNA that contain
specific instructions are called genes.
• Example would be regions of DNA that code for making proteins.
Huntingtin Protein• Cytoplasmic protein found in almost all
tissues of the body and brain
• Normal function is not well understood, yet implicated in cell membrane recycling and neuroprotection.
• Studies suggest that huntingtin protein regularly interacts with other proteins found in the brain
• The altered form of huntingtin protein leads to nerve cell death in brain.
Genetic Mechanism of HD: Unstable Trinucleotide repeat
• The gene responsible for causing HD is located in chromosome 4. The gene regulates the production of huntingtin protein.
• Huntingtin protein contains within it the amino acid glutamine (C-A-G). In people with HD, however, there is an excess number of glutamine.
• That is why HD is often referred to as a trinucleotide repeat disorder
HD = Huntingtin protein with expanded CAG (glutamine) tract
CAG repeat 10 – 35 in normal individuals More than 40 repeats in diseased patients
Proteins must be folded normally to function. Mutant expansion of CAG causes an unusual huntingtin protein which clumps together in the cell and causes neuronal cell death (in the brain only)
How much CAG expansion is too much?
• People with 10 to about 35 copies of CAG have a normal functioning form of the huntingtin protein.
• Expansion of 40 or more CAG repeats is often full penetrance and the person will develop HD.
• For people who have 36 to 39 copies of CAG, the outcome is less clear. Some will develop the symptoms of Huntington's disease and some will not.
Neuropathology of HD
• HD involve atrophy and cell death of the basal ganglia, the complex subcortical structures involved in control of motor movement, cognition and sensory pathways.
• Specifically, there is a progressive and marked degeneration of the caudate and putamen (striatum).
Neuropathology
• There are different types of neurons and neurotransmitters in the striatum, and the balanced interaction between dopamine, acetylcholine, and GABA play a vital role in regulating motor movements..
• Striatal gamma aminobutyric acid (GABA-ergic) medium spiny neurons are most vulnerable to cell death in HD..
• GABA normally has inhibitory effects on the thalamus and tells the cortex to ‘brake’ movement.
• Selective loss of these specialized cells result in decreased inhibition (i.e., increased activity) of the thalamus.
• Thalamus increases output to certain regions of the cerebral cortex. This may lead to the disorganized, excessive (hyperkinetic) movement patterns of chorea.
• As disease progresses, damage to other pathways and dopamine receptors causes a decreased stimulation to the cortex and thus rigid bradykinetic features.
Risk factor: GENETICS Altered chromosome 4
Overproduction of huntingtin protein
↓Clumping of huntingtin protein
↓Neuronal cell death in the basal ganglia
↓Imbalance of neurotransmitters in striatum (GABA)
↓Decreased inhibition of the thalamus
↓Disrupts critical interneural pathways
↓Thalamus increases output to regions of the cerebral
cortex
↓Excessive movement patterns of chorea
(Hyperkinesia)
↓Decreased stimulation to the cortex (bradykinesia)
Degeneration of Basal Ganglia
The brain of a person with HD has bigger openings due to death of nerve cells in that region
Brain Imaging studies in HD: Striatal degeneration and atrophy
• Caudate and putamen hypometabolism and volume loss begins before onset of symptoms.
• Some evidence of patchy cortical thinning are more prominent over the posterior cortical regions and proceed to the anterior cortical regions with disease progression, and more evident in the left striatum.
• Atrophy of thalamic subnuclei projecting to the prefrontal areas, substantia nigra, nuclei of hypothalamus, small regions of the hippocampus, and Purkinje cells of the cerebellum.
Clinical Features of Huntington’s Disease
• Progressive neurodegenerative disorder characterized by atrophy of the basal ganglia causing triad of cognitive, motor and psychiatric impairments. There is no cure for HD.
• Inherited autosomal dominant disorder with a 50% chance of inheriting the mutant gene from an affected parent.
• In western Europe and USA prevalence is higher at about 7-10 per 100, 000. Lower in Asian and African populations.
• Typically an adult onset disorder with a mean age onset of 35-44 years (range 2 to 80 years).
• <20% first display symptoms after age 50 and have a slower progression of the disease
• <10% of cases are juvenile HD with onset before age 20 years.
Survival after onset is 15-18 years (range 5-25 years) the average age of death is 54 years old.
Motor Abnormalities: Early/Mid HD
• Chorea – is the hallmark of the disease onset, present in most adult cases.
- may be caused by lack of appropriate reciprocal inhibition to the
muscle• Bradykinesia and rigidity often increases
causing inability to move or care for oneself.• Ocular motor disturbances may be seen in
as much as 75% of individuals.
• Subgroup of adult-onset HD patients has more predominant dystonia and rigidity, and paucity of chorea throughout the course of disease sometimes referred to ‘rigid-akinetic’ subtype.
Nsg. Dx: Self Care Deficit r/t uncoordinated movement and cognitive change.
Motor Speech Impairments: Hyperkinetic Dysarthria of Speech
• Oral mechanism exam often reveals normal structure, symmetry of face, lips, tongue, jaw and palate.
• Speech tasks such as conversation, oral reading, AMRs, vowel prolongation, are very useful to detect articulatory breakdown, rate and prosody changes, phonatory-respiratory discoordination
• Choreiform movements characterized by quick, unpatterned involuntary head/neck, jaw, face, tongue, palate, pharyngeal, laryngeal, and/or thoracic and abdominal movements at rest and during movement
• Dystonia or slower waxing/waning movements or posture
Skeletal (voluntary) muscles disorder characterized by weakness and easy fatigability due to autoimmune destruction of the AChR inthe postsynaptic membrane of theNMJ
Progressive muscle paralysis withoutsensory loss or atrophy.
Grade I: Focused and specific such as Ocular MS (weakness of the eye muscles)
Grade II a: Generalized mild weakness II b: Generalized moderate weaknessGrade III: Generalized severe weakness Grade IV: Myasthenia Crisis a severe
exacerbation of the disease and depletion of ACh receptors at the NMJ causing severe muscle weakness, respiratory insufficiency and SOB, extreme difficulty swallowing may cause quadriplegia or quadriparesis (incomplete paralysis).
Generalized autoimmune MGMyasthenia gravis has several courses:
1. Periodic remissions2. Slowly progressive course3. Rapidly progressive course4. Fulminating course (exploding in a sudden manner) Clinical presentation:Ocular muscle weakness
Orbicularis Oculi- muscle that controls eyelid movement
Reduced receptor by blocking,
degradation, damage
Reduced AChR density
Decrease binding of ACh to AChR
Diminished transmission of nerve impulses at NMJ
Decrease amplitude of AP
Failure in muscle fiber contraction
Weakness muscle(Voluntary)
IgG antibody interact AChR at the NMJ.
Masseter- jaw muscle used for chewing
Occular muscle weakness– Asymmetric
Usually affects more than one extraocular muscle and is not limited to muscles innervated by one cranial nerve
Weakness of lateral and medial recti may produce a pseudointernuclear opthalmoplegia
– Limited adduction of one eye with nystagmus of the abducting eye on attempted lateral gaze
– Ptosis caused by eyelid weakness– Diplopia is very common
Risk for Eye Infection r/t exposure of cornea
• Facial muscle weakness is almost always present
– Ptosis and bilateral facial muscle weakness
– Sclera below limbus may be exposed due to weak lower lids
Altered body image r/t changes in anatomical contour of the face & neck
• Basic physical exam findings– Muscle strength testing– Recognize patients who may
– Patients with MG have low numbers of AChR at the NMJ
– Ach released from the motor nerve terminal is metabolized by Acetylcholine esterase
– Edrophonium is a short acting Acetylcholine Esterase Inhibitor that improves muscle weakness
– Evaluate weakness (i.e. ptosis and opthalmoplegia) before and after administration
Steps:1. 0.1ml of a 10 mg/ml edrophonium solution
is administered as a test2. If no unwanted effects are noted (i.e. sinus
bradychardia), the remainder of the drug is injected
3. Consider that Edrophonium can improve weakness in diseases other than MG such as ALS, poliomyelitis, and some peripheral neuropathies
Complications of MG• Respiratory failure• Dysphagia• Complications secondary to drug treatment
– Long term steroid use• Osteoporosis, cataracts,
hyperglycemia, HTN• Gastritis, peptic ulcer
disease• Pneumocystis carinii
Guillain-Barré Syndrome
“Ascending Paralysis “AI-Destruction-Nodes of Ranvier
Acute inflammatory demyelinating polyneuropathy (AIDP) caused by an autoimmune disorder affecting the peripheral nervous system, usually triggered by an acute infectious process characterized by ascending paralysis.
Demyelination of Nerve Fibers Negative conduction abnormalities
- Slowed axonal conduction, variable conduction blocks occur in the presence of high- but not -low frequency volleys of impulse.
Positive conduction abnormalities- Generations of ectopic impulses, spontaneous
and abnormal “crosstalk” between demyelinated axons
Immunopathogenesis
Acute autoimmune disorder There is involvement of T and B
lymphocytes –↑cytokines and cytokine receptors in serum (IL 2, soluble IL 2 receptor) and CSF (IL 6, TNF α, interferon)
Brain is unable to send messages Legs and arms are commonly affected
Etiology
75% of cases are preceded by an acute infectious process usually GI or Respiratory in origin
20-35% of cases are preceded by a Campylobacter jejuni, HV, EBV infection.
Recent: swine influenza vaccine Destruction most often occurs in segments
between the Nodes of Ranvier
Why Nodes of Ranvier are the target of attack? Neural targets are likely to be gangliosides Gangliosides are complex
glycosphingolipids that contain one or more sialic acid residue
Gangliosides are present in large quantities in human nervous tissues and in key sites: NODES OF RANVIER
Pathophysiology of GBS
Etiology Autoimmue Campylobacter jejuni Virus
EBV HV SIV
B cells are activated by newly activated Th2 cells. This produces a cell-mediated and humoral response against the pathogen.
Migration to lymph nodes, a mature, differentiated APC activate CD4 T cells that
recognize antigen from the infectious pathogen
Molecular mimicry
Antigens enter into the body by multifenestrated cells
Innate immune response results in the uptake of the pathogens by immature APC
Production of antibodies and Phagocytosis of the bacteria
Cranial Nerves and Their Functions Test
No. Name General Function
Specific Function
I Olfactory Sensory SmellII Optic Sensory VisionIII Oculomotor Motor,
ParasympatheticMotor to four of six eye muscles and upper eyelid; parasympathetic: constricts pupil; thickens lens
IV Trochlear Motor Motor to one eye muscle
V Trigeminal Sensory, Motor Sensory to cornea face and teeth; motor to muscles of mastication
VI Abducens Motor Motor to one eye muscle
VII Facial Sensory,Motor, Parasympathetic
Sensory: taste; motor to muscles of facial expression; parasympathetic to salivary and tear glands
VIII Vestibulo-cochlear
Sensory Hearing and balance
IX Glossopha-ryngeal
Sensory,Motor, Parasympathetic
Sensory: taste and touch to back of tongue; motor to pharyngeal muscles; parasympathetic to salivary glands
X Vagus Sensory,Motor, Parasympathetic
Sensory to pharynx, larynx, and viscera; motor to palate, pharynx, and larynx; parasympathetic to viscera of thorax and abdomen
XI Accessory Motor Motor to 2 neck and upper back muscles
Lumbar PunctureIn lumbar puncture “LP” CSF is withdrawn through a needle inserted into the subarachnoid space of the spinal canal between the L3-L4 or L4-L5 lumbar vertebrae.
Measure CSF pressure determine viral or bacterial origin Increase in WBC count presence of cytokines (IL 6, TNF α,
interferon) Cx: inc. ICP → rapid decrease in pressure
within CSF around spinal cord→ brain herniation
Electromyography- Needle electrodes inserted into the muscle .- Pattern of electrical activity in the muscle
both at rest and during activity may be recorded.
- Relaxed muscles are normally electrically silent except in motor end plates.
- Abnormal spontaneous activity with denervation or inflammatory changes in the affected muscle.
The earliest description of MS was recorded in Holland on August 4, 142. But the history of the disease really begins in the 19th century with the first clear illustrations and clinical description of the disease beginning to appear in 1838.
The first actual case was diagnosed in 1849. It was Dr. Jean-Martin Charcot who is credited for giving the first signs and symptoms of Multiple Sclerosis.
Multiple Sclerosis - Epidemiology Worldwide occurrence:1.1 – 2.5 million
cases Female: male ratio = 2:1 In Canada an estimated that 55,000-75,000
people have multiple sclerosis Affects nearly 500,000 individuals in the US Occurs most frequently between ages 25 –
35
Genetic and the Immune System
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ImmuneResponseGenes
Factors Contributing for MSGenetic Factors
Gender: Women are 2 to 3 times more likely to get the disease.
Family history of MS: A family history increases the risk
Race: MS appears more in Caucasians than in other groups
Environmental factors Latitude: As you increase latitude, mainly
above and below 40° latitude. MS is more common. It is five times more likely in temperate and cooler climate regions.
Socioeconomic status: Least common in rural and lower class.
Migration: The age at which you may move may also be an important factor. “If you move before the age of 15, your risk is likely to that of the people in the country you move to. If you move after the age of 15, your risk stays fixed at that of the country you grew up in”.
Infection : “They believe MS is a delayed reaction to a viral infection contracted during childhood by a genetically susceptible person” (O’Connor 13). The viral infections may include shingles, chicken pox, measles, or certain herpes. An idea they also have concerns the age at which you get the infection. The older you are the higher the risk for MS.
***Remember that in warm countries, children contract viruses at a younger age.
Not Everyone with a Genetic Risk Will Develop MS – Why?
Risk is modified by Environmental factorso Sunlighto Diet (e.g., vitamin D)o Other lifetime experiences
(infections?)
Multiple Sclerosis - Causeso The exact cause of multiple sclerosis is not clearo MS patients, have a higher number of immune
cells which suggests there might be an immune response; this is suspected to be due to a virus or genetic defect
o Other causes are environmental and hereditary
How Does it work?
Demyelination of Nerve Fibers in MS Positive conduction abnormalities generations of spontaneous ectopic impulses and
blocks occur in the presence of high- but not -low frequency volleys of impulse.
The destruction of the myelin sheath leads to impaired communication between nerve cells
Mode of Action The immune system attacks axons,
causing destruction of the myelin sheath resulting in a Conduction Block which leads to permanent loss of function.
MS is an Immune-Mediated DiseasePathophysiology
Autoimmune response results in damage and loss of fibers.
Nerves can regain myelin, but the process is not fast enough to avoid the deterioration that occurs
Astrocytes form scars where myelin formerly existed
Inflammation, loss of myelin of nerve fibers, and the scarring that follows result in reduced transmission of nerve signals within the CNS.
Type of symptoms and severity vary widely due to the location of the scar tissue and the extent of demyelination
Multiple Sclerosis Signs and Symptoms Vision impairment Lhermitte‘s sign- momentary paresthesia Difficulty in walking Weakness and exhaustion Memory loss Depression Urinary and bowel problems + Babinski’s reflex
Nursing Diagnosis1. Pain chronic r/t stimulations of free nerve
ending 2 to destructions of myelinated axons.
2. Impaired sensory perception r/t nonsynaptic 3. transmission of demyelinated axons. 4. Fatigue r/t decrease energy production5. Paralysis r/t conduction block of demyelinated
axons.6. Low self Esteem r/t change in brain
structure/function. 7. Ineffective coping r/t multiple life changes. 8. Risk for care givers role train r/t severity of
the care receiver, duration of care giving required
9. Deficient knowledge regarding condition, prognosis, complications, treatment and need r/t unfamiliarity of information resources.
Multiple Sclerosis - TypesThere are 4 major types of MS
Relapsing-remitting MS (RR-MS) Primary-progressive MS (PP-MS) Progressive-relapsing MS (PR-MS) Secondary-progressive MS (SP-MS)
Relapsing-remitting MS (RR-MS) More than 80% Defined clinical exacerbation of neurological
symptoms Followed by complete or incomplete
remission during which the person fully or partially recovers from the deficits acquired during relapse
Primary-progressive MS (PP-MS) 10 to 20% Gradual progression of the disease No overlapping relapses and remissions
Progressive-relapsing MS (PR-MS) Rare Initially presenting as PP-MS, however during
the course of the disease the individuals develop true neurologic exacerbations
Steady progression of clinical neurological damage with superimposed relapses and remissions.
Secondary Progressive MS (SP-MS) SP-MS is characterized by a steady
progression of neurological damage with or without superimposed relapses and minor remissions
Individuals with SP-MS will have experienced a period of RR-MS, which may have lasted from 2 to 40 years
Any super-imposed relapses and remissions fade over time
How Is MS Diagnosed? At least two episodes of symptoms
a) Occur at different point in timeb) Result from involvement of different areas
of the central nervous system Absence of other treatable causes for the
symptoms Results of neurological testing
DIAGNOSTIC WORKUPRadiologic studies
It is diagnosed by neurological examination and brain MRI scans
o Signs of two separate attacks with demyelination of CNS supports the diagnosis.
Magnetic Resonance Imaging (MRI)Is a noninvasive diagnostic scanning technique in which the client is placed in a magnetic field. MRI provides a better contrast between normal and abnormal tissue than the CT scan. For visualization of the brain, spine, limbs, and joints, heart, blood vessels, abdomen and pelvis.
Brain Atrophy (Shrinkage) in Untreated MS
Images acquired over the course of 7 years from a single person with untreated MS Brain atrophy is seen as the enlargement of the ventricle and sulcal spaces. In untreated MS, by year 2, up to 6% of brain volume can be lost.
Serum and CSF Analysis
Blood tests Lumbar Puncture (spinal tap)
- If MS is present, persistent elevated of CSF protein IgG (oligoclonal antibody) bands can be seen in spinal fluid which is an additional confirmatory test.
Symptom Management – Examples Pain control Management of impaired bladder and bowel
function Anti-spasmodic drugs Treatment of fatigue Splinting for contractures Counseling
CNS TUMOR
Glioma Stem cells are unspecialized immature cells that can renew themselves through cell division for long periods of time.
** A glioma is a type of tumor that start in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain. Types of CNS tumor
n Intracranial n Intraspinal
Main Types of Brain Tumor Primary – tumor starts in the brain Types of Primary Tumor 1. Benign - do not contain cancer cells 2. Malignant- do contain cancer cells.
Metastatic – Tumor starts somewhere else in the body.
Cell Types and Associated Tumors of the Central Nervous System.
GLIOMAS
Classification:Astrocytomas from astrocyte, invasive, slow growing in the brain and spinal cord Glioblastoma Multiforme extremely malignant, highly vascular tumors that arise from undifferentiated astrocytomasOligodendrocytomas
Cell Type Function Associated Tumors
Astrocyte
Provides nutrition, insulation,and structural support for neurons
NeuronConducts electrical signalswithin neural systems
GangliogliomaGangliocytomaCentral neurocytoma
Oligodendrocyte Provides insulation to neuronal axons to facilitate signal conduction
OligodendrogliomaOligoastrocytoma
Ependymal cell Forms lining of the ventricularSystem
Ependymoma
from oligodendroglia, avascular, encapsulated, malignant form is oligodendroblastomaEpendymoma from ependymal cells, more common in children, malignant form is called ependymoblastoma.
Grading Low-grade - Well-differentiated (benign)
with a better prognosis.
High-grade - Undifferentiated (malignant) with worst prognosis.
WHO grading system for astrocytoma GRADE 1 Least malignant and slowest to grow. If they are surgically totally removed they can be associated with long-term remission.
GRADE 2 Have more malignant cells in them, they grow faster and have the tendency to recur, often more cancerous than the first time.
GRADE 3 Malignant cells undergoing mitosis, infiltrating and may recur at a higher grade.
GRADE 4 A tumor are very malignant and are often difficult to treat, also known as Glioblastoma Multiforme, usually requires operation to take as much tumor as possible followed by radiation therapy and sometimes chemotherapy
Another Grading SystemEarlier Stages GRADE I
GRADE IIGRADE III
Advanced Stages GRADE IV
LocationSupratentorial Above the tentorium, in the cerebrum, most common in adults.
Infratentorial Below the tentorium, in the cerebellum, most common in children. Neural stem cells are multipotent and self- renewing, have been isolated from the subventricular zone,
GLIAL PROGENITOR CELLS — self-renewing precursors capable of producing astrocytes and oligodendrocytes
INTRASPINAL TUMORSClassified according to location in relation to the dura and spinal cord
Extradural- arising from the extradural space
Intradural - originating within the neural tissue. 1. Extramedullary arising from the blood vessels, meninges or
nerve roots, forming an intradural tumor Neurofibromas (Nerve sheath tumor) grow in the nerve root that extends into the extradural space Meningiomas tumor originates from the dura matter and
arachnoid membranes
2. Intramedullary tumors arising from within the substance of the spinal cord itself Ex. Ependymomas, Astrocytomas, Glioblastomas, Oligodendrogliomas, Ganglioneuromas, Medulloblastomas, Hemangioma, Hemangioblastomas
RISK FACTOR Genetics
- Cells contain genetic material called chromosomes.
- Controls growth of the cells- When the genetic material becomes
abnormal, it can loose its ability to control its growth.
Infections Diet: Nitrate C Exposure to Chemicals: Formaldehyde Vinyl Chloride Acrylonitrile
Multi hit hypothesis Cellular telephones Exposure to high tension wires Hair dyes Head trauma
neuromuscular deficit with loss of sensory reception and transmission.
- Impaired Urinary Elimination r/t loss of nerve conduction above the level of reflex arc.
DiagnosticsBone Scan PET scan CT- guided needle biopsy Open biopsy
Parkinson’s Disease (PD)Dopamine depletion-
Substantia Nigra
Degenerative disorder resulting in dysfunction of extrapyramidal system caused by dopamine depletion which interferes with inhibition of excitatory impulses.
Extrapyramidal pathways: cerebral cortex, thalamus, cerebellum and brain stem.
Nitroglial dysfunctions produce by syndrome of abnormal movement called Parkinsonism.
Extrapyramidal Tracts: uncrossed tract of motor nerves from the brain to the anterior horn of the spinal cord. Within the brain extrapyramidal pathways comprise of various relays of motorneurons between motor areas of cerebral cortex and basal nuclie, the thalamus, the cerebellum and brain stem.
Historical PerspectiveDr. James Parkinson (1755-1828)- 1817
“involuntary tremulous motion”
“pass from a walking to a running pace”
“shaking palsy”London home
EpidemiologyAve. age of onset 60Men and women affected equally but more prevalent in malesGenetic Link—chromosomes 4Environmental Toxin (MPTP)African-Americans and Asians less likely than Caucasians to develop Parkinson’s
they can advance. They walk with small shuffling steps, have no arm swings, and may have difficult in stopping. Some patient may walk with festinating gait example: at an increasing speed to prevent themselves from falling because of there center of gravity.
Characteristic Problems
Hypophonia-soft speechDysarthria-unclear pronunciation Festination-shuffling gaitMicrographia – small handwriting
* The combination of tremor, rigidity and bradykenisia result in small tremolous and often eligible handwriting. Patients have difficulty in writing or and hand to assume flexed posture when erect.
Hypomimia – decreased facial animationBlepharospasm – involuntary eyelid closureBlepharoclonus – fluttering of close eyelidsMyerson’s sign – tap in between eyebrows
Hoehn and Yahr Staging of Severity of Parkinson’s Disease
Stage Description
0 No clinical signs evident
I Unilateral involvement
II Bilateral involvement but no postural abnormalities
III Bilateral involvement with mild postural imbalance on examination or history of poor balance or falls; patient leads independent life
IV Bilateral involvement with postural instability; patient requires substantial help
V Severe, fully developed disease; patient restricted to bed or wheelchair
7. Risk for aspiration related to impaired muscles of swallowing
8. Risk for falls related to impaired gait and balance.
Diagnosis
History and Physical examinationBradykinesia must be present with atleast two
of the following: limb muscle rigidity, resting tremor, or postural instability.
Diagnostics Radiologic study
No specific diagnostic available (PET) Positron Emission tomography
- Computerize tomographic technique that uses radioactive substance to examine metabolic activity of various structures.
- given by inhalation or injection. - Radioactive (FDG) Fluoro-2- deoxy-D-glucose.
HEAD TRAUMA
Neurologic Assessment Levels of consciousness Glassgow coma scale Cranial nerve assessment
Definition – Traumatic Brain Injury (TBI) - is a result of an external mechanical force to the brain that leads in a change to cognitive, physical, psychosocial functioning associated with altered state of consciousness. The impairments can be temporary or permanent.
Risks Factor FallsFirearms
Traumatic Brain Injury Primary Brain Injury
Movements of brain inside skull
Brain damage and nerve injuries result in frequent and severe
headache
Brain floating with CSF
External forces transmitted to the brain
Direct injury to brain tissue
Results from what has occurred to the brain at the time of the injury
Secondary Brain Injury Physiologic and biochemical events which
follow the primary injury
Categories of Brain Injuries Closed (Blunt) Brain Injury
Acceleration/Deceleration If a moving object hits a movable
head (e.g. head gets hit with a bat) If a moving head hits something
stationary Shaken type of movement
(E.g., when head rocks back and forth in skull).
Non-Acceleration Much more rare, referred to as a
crushing injury If a moving object hits a head that is
fixed (e.g. car falls on head while you are working under it).
Categories of Brain Injuries Open Brain Injury
Low Velocityo Skull is no longer intact, part of
skull or debris gets into the brain.
High Velocityo Bullets penetrate the skull and
goes into the brain matter.
CAUSES OF BRAIN INJURIESCoup and Countercoup InjuriesConcussion vs ContusionDiffuse Axonal InjuryEpidural HematomaSubdural HematomaIntracerebral HemorrhageCompound fracture Penetrating injury
COUP The energy of impact from a small hard object tends to dissipate at the impact site, leading to a COUP contusion
COUNTERCOUP Impact from a larger object causes less injury at the impact site, since the energy is dissipated at the beginning or end of the head motion.
Contusion
Bruising type of injury to the brain resulting to sudden loss of consciousness or coma. Contusion may occur with subdural/ extradural collection of blood, intracerebral hemorrhage.
Contusion is considered severe form of axonal injury with shearing of blood.
Concussion
Mild bruising to the cerebral tissue cause by jarring of the brain resulting in transient loss of consciousness. Concussion is considered a mild form of diffuse axonal injury
Categories of Diffuse Brain Injury
Mild Concussion (without LOC) Grade I confusion disorientation with
amnesia Grade II confusion and retrograde amnesia
(5-10 min) Grade III confusion with retrograde and
anterograde.
Immediate but transitory clinical manifestation.
CSF pressure rises, ECG, EEG changes. Confusion last for several minutes. with amnesia for events preceding the
trauma. Head pain, nervousness and not being
themselves.
(grade IV) Classic Cerebral Concussion diffuse cerebral disconnection from
brain retrograde and anterograde amnesia May experience post-concussive
syndrome
Vital signs quickly stabilized Confusion for hours to days Head pain, fatigue, nausea, inability to
concentrate and Forgetfulness, mood and affect changes
Diffuse Axonal InjuryDiffuse axonal injury is characterized by extensive generalized damage to the white matter of the brain
Strains during high-speed acceleration/deceleration produced in lateral motions of the head may cause the injury.
Categories of Diffuse Brain Injury DAI Mild (coma > 6 -24 hrs) Persistent residual cognitive, phsychologic, sensorimotor deficit
Decorticate and decerebrate posturing Experience prolonged period of stupor Permanent deficit in memory, attention,
abstraction, reasoning, problem solving, executive function, vision or perception and language
Decorticate
Decerebrate
Moderate Widespread impairment cerebral cortex, diencephalon, tearing of axons both hemispheres
Transitory decortication or decerebration Unconsciousness lasting days or weeks On awakening the person is confused and
suffer long period of post-traumatic anterograde and retrograde amnesia
Severe (LOC > week)Severe mechanical disruptions of axons in both hemisphere, diencephalon and brain stem
Immediate autonomic dysfunction that disappear in few weeks
IICP 4-6 days after injury compromised coordinated movements with
verbal and written communication, inability to learn and reason, inability to modulate behavior
Compound Fracture
Object strikes the head with great force or head strike the object forcefully temporal or occipital blow upward impact of cervical vertebrae (basilar skull fracture)
Penetrating Injury
Missile (bullets) or sharp projectile (knives, axes, screwdriver)
Children younger than 5 Pregnancy Working with animals Compromised immune system
Pathophysiology:
Bacteria reach the meninges through: Bloodstream Direct contact between the meninges
through either the nasal cavity or the skin
Bacterial Meningitis
Mechanism of invasion is not completely understood
Host defense mechanisms within the CSF are often ineffective.
Bacterial proliferation stimulates a convergence of leukocytes into theCSF.
Meningeal and subarachnoid space inflammation
release of cytokines into the CSF (TNF, interleukin 1, 6)
Complications of Bacterial Meningitis (IMMEDIATE) Dehydration Pericardial Effusion Death coma loss of airway reflexes seizures cerebral edema vasomotor collapse DIC Respiraytory arrest
Complications of Bacterial Meningitis (DELAYED) Snhl Ataxia Blindness
‡ Inflammation of the brain parenchyma, present as diffuse and/or focal neuropsychological dysfunction most commonly a viral infection with parenchymal damage varying from mild to profound.
Etiology Arboviruses and herpes simplex virus are
the most common causes of endemic and sporadic cases of encephalitis, respectively.
Varicella, herpes zoster and Epstein-Barr virus - cause of encephalitis in uncompromised hosts. ‡
Severe and Fatal Encephalitis-Arthropodborne viruses and HSV
Viral replication
Hematogenous spread to CNS ‡ Retrograde transmission along
neuronal axon Direct invasion of the subarachnoid
space through infection in the olfactory submucosa
Vectors and Reservoirs
Humans are the reservoir for enteroviruses, mumps, measles, herpes simplex, and varicella viruses.
H. capsulatum and C. neoformans are organisms found in soil contaminated with bird droppings
Vectors and Reservoirs Cats are the definitive host for T.
gondii; they acquire the parasite from eating infected rodents or other infected meat.
Monkeys are the reservoir for simian B virus (cercopithecine herpesvirus 1).
Modes of Transmission
Enteroviruses: transmitted from person to person through ingestion of materials
contaminated by the feces of an infected person
through exposure to infectious respiratory droplets
indirectly via fomites
Some causes of encephalitis, such as Listeria sp. and T. gondii, may be acquired through consumption of contaminated food
Measles and varicella viruses are transmitted from person to person through airborne route.
Simian B disease is transmitted to humans: through monkey bites exposure of naked skin or mucous
membranes to infectious monkey saliva or monkey tissue culture