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>IMUEOS gets around 15k uniques per month! (For readers, sponsors and advertisers)

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Hi everyone!
It’s been sometime since I’ve updated this medical blog. I hope it has served you well in your medical studies as much as it did for myself. Good news, I have completed my phase 1 medical studies (MBBS) or equivalent to USMLE Step 1.
Due to my hectic schedule, I haven’t managed to put on a better template for this blog. It also seems that the Google Site Search’s pretty messed up as well. However, lookout for a major revamp soon! I will try to make this blog more user friendly, so that lecture notes can be easily found.
So far, there are basic sciences lecture notes on all organ systems except Cardiovascular, Respiratory, Haematology and Gastrointestinal Systems. That will probably take some time for me to update, probably after the blog revamp. I will also be starting off a mailing list and twitter account so that you guys can get notified for any updates as well as quiz and tips!
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STATS & ANALYTICS
Here’s my blog analytics from 8th February to 6th March 2011:
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My blog’s average is around 4,000 uniques per week and can reach up til 20,000 uniques per month. These are from returning visitors as well as referred first time visitors from search engines and other sites.
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61% of visitors are from the United States – so the syllabus covered in this blog is relevant to USMLE students as well.
Do drop me an e-mail at terrichan88@gmail.com – even just a howdy!

Behavioural response to exercise

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Topics covered:

  • Problems with sedentary lifestyle
  • Benefits of changing lifestyle
    • enhance daily function
    • maintain reserve capacities
    • prevent diseases
      • diabetes
      • osteoarthritis
      • heart disease
    • decrease effects of age and chronic diseases
  • Hazards of strenuous exercise
    • heart attack
    • amenorrhea
    • osteoporosis
    • infertility
    • suppresses immune system (when already sick)
    • back & shoulder pain
    • dehydration
    • hyperthermia (overheat – heat stroke)
    • injury from high impact exercises
  • Prevention of problems with strenuous exercise
    • Appropriate footwear
    • improving coordination
    • alternate easy & harder workouts
    • warm up, cool down
    • stretching
    • take days off
    • food rich in antioxidants (Vit. A, C & E)
  • Risk factors – strenuous exercises
    • Asthma
    • Cystic fibrosis
    • Diabetes

Impairment & disability

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Impairment

  • any loss or abnormality of psychological, physiological or anatomical structure or function

Disability

  • any restriction or lack (resulting from an impairment) of ability to perform an activity
    • in the manner or within the range considered normal for a human being

Handicap

  • disadvantage for a given individual, resulting from an impairment or a disability,
    • that prevents the fulfillment of a role that is considered normal (depending on age, sex and social and cultural factors) for that individual

Nature of disability

  • Time of onset
    • infancy
    • later in life
  • Functions impaired
  • Severity of disability
  • Visibility of disability
  • Stability of disability
  • Pain

Stages of accommodation

COHN’S 5 stages in adjustment process

  1. Shock
  2. Expectancy of recovery
  3. Mourning
  4. Defence
  5. Final adjustment

Stages of family adjustment (response to child’s disability)

  1. Withdrawal/rejection
  2. Denial
  3. Fear & frustration
  4. Adjustment

Devaluation of disability – Why?

  1. Attitudinal barrier
  2. Overvaluation of physique
  3. Blaming the victim
  4. Insistence of mourning

Discrimination

Many persons with disabilities-feel-their problems stems primarily from

  • prejudice
  • discrimination

Labelling

  • Name-calling by non-disabled person

Local & General anaesthetics

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*Read written notes.

Local anaesthetics – Musculoskeletal system

General anaesthetics – Nervous system

Sedative hypnotics & anticonvulsants

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*Refer written notes

Drugs acting on neuromuscular junction

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*Refer written notes

Pathology of peripheral neuropathies

2

Tests for peripheral neuropathy

  • Electromyography
    • measures electrical impulses in muscle at rest & when contracting
    • Differentiates between muscle and nerve disorders
  • Nerve conduction velocity
    • assess the degree of damage in the larger nerve fibres due to myelin loss
    • Slow transmission –> myelin damage   
    • Decrease strength of impulse -> axonal degeneration
  • Nerve biopsy
    • invasive
    • sural nerves (unmyelinated nerve)
  • Skin biopsy
    • assess damage present in small fibres
    • nerve conduction tests cannot assess these

Approach to peripheral nerve diseases

Consider whether the pathology is:

  • Primary damage to Schwann cells/myelin
    • Acute inflammatory demyelinating polyradiculoneuropathy (GBS)
    • Chronic inflmamatory demyelinating polyradiculoneuropath
    • Paraprotein neuropathy
    • Charcot-Marie-Tooth type 1
  • Damage to neuron/axon
    • Damage affecting predominantly small unmyelinated fibres 
      • amyloid
      • diabetes mellitus
      • HIV
    • Affecting all axonal population
      • vasculitis
      • CMT type 2

Pathology of demyelination

  • Axon damaged
  • Neural bodies intact
  • Conduction block
    • conduction velocity decreases

Patterns of axonal pathology

  1. Wallerian degeneration
    • In transected axon
      • distal portion undergoes disintegration & degradation
    • Limited recovery & regeneration
    • Neuronal body
      • chromatolysis
        • activation of protein synthesis to help regenerate axon
    • Examples:
      • trauma
      • infarction
        • diabetic mononeuropathy
        • vasculitis
      • neoplastic infiltration
  2. Distal axonopathy
    • Degeneration of axon and myelin starts in the most distal part of the axon
    • Axon dies back (retrograde)
      • ‘stocking-glove’ sensory
      • motor deficit
    • Caused by neuronal body pathology
      • resulting in inability to sustain the metabolic needs of the axon
    • Examples
      • drugs
      • toxins
      • organophosphates
      • diabetic polyneuropathy*
      • alcohol
      • vitamin deficiency
      • uraemia
      • malignancy

Classification of peripheral neuropathy

By etiology

  1. Inflammatory neuropathies
    • Immune-mediated
    • Examples
      • Gullain-Barre Syndrome
      • chronic inflammatory demyelinating polyradiculoneuropathy
  2. Infectious
    • Examples
      • Leprosy (Hansen’s disease)
      • Diptheria
      • Varicella-zoster
  3. Hereditary
    • Examples
      • Charcot-Marie-Tooth 1,2 and X
  4. Acquired metabolic & toxic neuropathies
    • Examples
      • Diabetes mellitus
      • vitamin deficiency
      • liver disease
      • alcohol
      • malignancy
      • paraneoplastic

By site of pathology

  • Affecting Schwann cells/myelin
    • Acute inflammatory demyelinating polyradiculoneuropathy (GBS)
    • Chronic inflmamatory demyelinating polyradiculoneuropathy
    • Paraprotein neuropathy
    • Charcot-Marie-Tooth type 1
  • Affecting the neurons/axons
    • Damage affecting predominantly small unmyelinated fibres 
    • Example
      • Amyloid
      • Diabetes mellitus
      • HIV
  • Affecting all axonal population
    • Vasculitis
    • CMT type 2

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DEMYELINATING DISEASES

Acute inflammatory demyelinating polyradiculoneuropathy

  • General
    • Also known as: Guillain-Barre Syndrome
    • T-cell mediated immune response & humoral response
  • Clinical features
    • Rapidly evolving
      • Ascending symmetrical weakness
      • Areflexia
    • Variable autonomic dysfunction
    • Mild sensory sign
    • Mostly preceded by an acute flu-like illness
      • complication of influenzae infection
  • Important features
    • Ascending paralysis
    • Loss of deep tendon reflexes
    • Decreased nerve conduction
    • Increase in CSF protein
      • Little cell increase
  • Infectious agents implicated include
    • Campylobacter jejuni
    • CMV
    • EBV
    • Mycoplasma pneumoniae
    • Influenzae virus
  • Microscopic pathology picture:
    • Endoneurial lymphocytic inflammation
      • macrophage infiltration
      • MACROPHAGE mediated DEMYELINATION
    • More severe in the nerve roots
      • more subtle in the periphery
      • Axonal damage when disease is severe
    • Electron microscopy
      • macrophage penetrating basement membrane of Schwann cells
      • Stripping myelin sheath away
      • Remyelination can occur
  • Plasmapharesis is effective in some cases

image

Chronic inflmamatory demyelinating polyradiculoneuropathy

  • Classical Triad
    • Symmetrical proximal & distal weakness
      • for more than 2 months
    • Loss of large fibre modalities
    • Loss of deep tendon reflexes

  • Laboratory studies
    • Endoneurial inflammation
    • Onion-bulb formation in semithin sections
      • due to repeated demyelination & remyelination

Hereditary Sensory and Motor Neuropathy (HSMN)

  • General
    • Also known as Charcot-Marie-Tooth type 1
  • Clinical features
    • Slowly progressive distal weakness
    • Usually begin in childhood
    • Muscle atrophy and sensory impairment
    • Dominance of distal lower extremities signs and symptom
    • Hammertoes
    • Pes caves
      • high arch
    • Nerve enlargement (hypertrophy)
      • If nerves palpable and tremors = CMT type 1
    • Very slow disease with normal longevity
  • Pathology
    • Decrease numbers of large & small myelinated fibres
    • Onion bulb formation
    • Increase in calibre of affected nerves
      • nerve hypertrophy
    • Axonal form (CMT2)
      • no onion bulb, but regenerative axonal clusters
    • Genetic mutation of myelin related proteins

Paraprotein neuropathy

image

  • Neuropathy associated with a monoclonal gammopathy
  • Incidence
    • > 50 yrs
    • male
  • Clinical features
    • Mild slowly progressive symmetrical distal weakness
    • Painful with severe sensory loss & paresthesia
  • Diagnosis
    • Monoclonal IgM with anti-MAG (myelin-associated glycoprotein activity)
  • Pathology
    • Non-specific myelin & axonal loss
    • POEMS syndrome
      • polyneuropathy
      • organomegaly
      • endocrinopathy
      • M protein
      • skin changes

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AXONAL DISEASES

Amyloid neuropathy

  • General
    • Hereditary/acquired
  • Important features
    • Small fibre neuropathy
      • pain
      • temperature
      • autonomic dysfunction*
  • Clinical features
    • Painful dysesthesias
    • Bowel & bladder dysfunction
    • Impotence
    • Orthostasis
    • Cardiac & renal abnomalites
  • Pathology
    • Biopsy abdominal fatpad
      • Amyloid deposition in endomerium & vascular wall
      • Large myelinated fibres are preserved

image

Diabetic polyneuropathy

  • Cause
    • diabetes mellitus
  • Most common pattern
    • length-dependent axonal sensorimotor polyneuropathy
  • Manifest as
    • PAIN and PARESTHESIAS
  • Clincal features
    • Start in distal lower extremities
      • longest nerve fibres
    • Gait abnormality
    • Autonomic abnormality
      • ‘diabetic autonomic neuropathy
    • Sensory dysfunction distal extremity
      • glove & stocking numbness
    • weakness of distal lower extremity
  • Pathology
    • Axonal neuropathy
    • Loss of large, small & unmyelinated fibres
    • Entirely NON-SPECIFIC
  • Pathophysiology
    • Nerve ischaemia
      • due to diabetic microangiopathy
      • poor blood flow
      • may easily develop ulceration

image 

  • Skin biopsy to assess small-nerve fibres
    • Easy to perform
    • Provides information on small nerve fibres
      • not possible with sural nerve biopsy
      • nor with routine neurophysiological testing
    • Can demonstrate subclinical neuropathy
      • eg. in diabetic patients

image

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Hansen’s disease

  • Causal organism
    • Mycobacterium leprae
  • Pathology
    • In Lepromatous leprosy
      • Schwann cells are invaded by the mycobacteria
      • Increase in Th2 cytokines: IL3, IL5, IL10
      • Increase CD8 cells
    • In Tuberculoid leprosy
      • active cell mediated immune response
        • injures cutaneous nerves
        • including axons, schwann cells & myelin
      • Increase Th1 cytokines: IL2, IFNγ, TNFβ
      • Histology:
        • granulomatous inflammation, scanty bacilli
  • Clinical features
    • Pain fibres affected
      • loss of sensation

Traumatic neuroma

  • Non-neoplastic
  • Occurs at proximal end of severed nerve
    • trauma
    • surgery
  • Clinical features
    • Firm nodule, painful or tender
      • Reactive proliferation of schwann cells, axons & fibrous ce
        lls

Tumours of peripheral nerves

Neurofibroma

image

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  • Cutaneous/ in Peripheral nerve
  • Plexiform type
    • only seen in Neurofibromatosis Type1 (NF1)
  • Tumours in NF1 are more likely to become malignant
    • Malignant tumours are called
      • Malignant Peripheral Nerve Sheath tumours (MPNST)
  • Histology
    • Spindle shaped cells
    • Serpentine nuclei
    • Schwann cells, axons, fibroblastic cells and perineurial cells are present

Schwannoma

image

  • Arise from Schwann cells
  • Histology
    • True encapsulation
    • Antoni type A & Antoni type B areas
    • Verocay bodies
  • Multiple tumours seen in NF2
    • Benign
  • Malignant counterpart is MPNST

Leprosy & Poliomyelitis

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  • Definition
    • A chronic bacterial disease of the skin, peripheral nerves and the upper airway
  • One of the most feared diseases
  • Causal organism
    • M. Leprae
  • Early stage
    • painless depigmented patch

Differential diagnosis

  • Tinea vesicolor
  • Pityriasis rosea
  • Birth mark depigmentation
  • Granuloma multiforme
  • Psoriasis
  • Contact dermatitis
  • Avitaminosis B
  • Neurofibromatosis
  • Scleroderma
  • Xathomatosis

image

Epidemiology

  • Infectious agent:
    • Mycobacterium leprae
      • acid fast bacilli
      • cannot grow in bacterial media/culture
      • Grow on
        • mouse foot pads
        • in nine banded armadillo
  • Occurrence
    • World prevalence 10-12 million
    • Prevalence rates >5 per/1000 rural tropics and subtropics
  • Endemic areas
    • SE Asia
    • South Asia
    • Philippines
    • Indonesia
    • India
    • Bangladesh
    • Pacific Islands
    • Tropical Africa
    • Latin America
  • Reservoir
    • Man is the only reservoir of proven significance
    • Feral Armadillos in Louisiana & Texas are affected
    • Naturally acquired leprosy Manageby monkey & chimpanzee
      • captured in  Nigeria and Sierra Leone\

Mycobacterium leprae

  • General
    • Acid fast
      • occurs in intracellular and extracellular
    • Occurs in clumps or bundles
      • globi
    • Affinity for
      • Schwann cells
      • cells of the reticulo- endothelial system
    • They remain dormant in various sites
      • can cause relapse
    • Leprosy is highly infectious disease
      • but low pathogenecity
  • Mode of transmission
    • Contact
      • not clearly established
        • Household
        • prolonged close contact
    • Droplet infection
      • Millions of bacilli are liberated daily
        • in the nasal discharge
          • remain viable for 7days in dried nasal secretions
        • Cutaneous ulcers also shed large amounts of bacilli
  • Incubation Period
    • 9 months – 20 years
      • average 4 years for tuberculoid
      • 3-5  years for lepromatous
    • Disease seen children <3 years
      • 50 cases so far
      • youngest: 2 1/2 month
  • Period of communicability
    • Infectivity is lost in most instances (continuous & regular treatment)
      • within 3 months
        • with Dapsone (DDS) or clofazimine
      • within three days
        • with rifampine
  • Susceptibility and resistance
    • Persistence and form of leprosy depend upon ability to develop cell mediated immunity
  • Lepromin test
    • Intradermal injection of autoclaved M.  Leprae & the presence or absence of induration at 28 days is called Mitsuda reaction
    • Reaction
      • lepromatous leprosy
        • -ve immune reaction
        • Mitsuda reaction
      • tuberculoid disease
        • +ve immune reaction
    • The test gives prognostic information but it is not diagnostic

image

Intermediate lesion

  • Small macules
    • irregular
    • raised edge
    • pale skin lesions
    • anywhere on the body
      • Most common on
        • back
        • forearm
        • thighs
        • face
  • No sensory loss
  • Normal sweating
  • Pathology –non specific inflammatory reaction
  • 90% spontaneous recovery
    • may progress to any of the three later types
    • depending on the cell-mediated response
      • Tuberculoid leprosy
      • Lepromatous leprosy
      • Borderline leprosy 

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Tuberculoid leprosy

image

  • Clinical features
    • One or more sensationless  asymmetrical macules with raised edges
      • In dark skins macules: depigmented
      • in pale skins macules: reddish
    • Affected nerves are thickened
      • ulnar
      • median
      • superficial radial
    • Loss of sweat
    • Loss of sensation
    • Wasting of muscles
  • Skin smear
    • -ve for M. leprae
  • Biopsy shows
    • epithelial granuloma with giant lymphocytes
    • scanty bacilli

Lepromatous leprosy

image

  • Clinical features
    • Numerous symmetrical distributed, macular, plaque form/nodular skin lesions
      • Leonine facies
        • lion face
      • Skin thickened by infiltration
      • Swelling of nose, ear and lips
    • Proliferation of infection in mucous membranes
      • causes nasal congestion & keratitis
      • Nasal discharge, painful eyes
    • Peripheral neuritis
      • complicated by neuropathies ulcers on limbs
      • lead to disfiguration and disability
    • Loss of sensation, pain and temperature
    • Neuropathic ulcers on
      • hands, feet
      • with loss of fingers and toes
    • Painless burns or ulcers
      • Secondary infection
    • Facial nerve palsy
    • Testis & lymph nodes may be damaged
    • Generalized systemic symptoms
      • fever
  • Skin smear highly +ve for bacilli
  • Immune response highly -ve (Mitsuda reaction)

Borderline leprosy

image

  • between tuberculoid & lepromatous
  • Mixed clinical features
    • Skin lesions often raised ring shaped lesions
      • with normal or slightly reduced sensation
    • Peripheral nerves may be thickened

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Clinical manifestations

  • Signs of peripheral nerves involvement
    • Skin lesions
      • Test for light touch, pin prick & temperature discrimination
      • Hyperesthesia & anesthesia
    • Peripheral nerves
      • Bilateral palpation of peripheral nerves for enlargement and tenderness
        • ulnar at elbow
        • peroneal nerve at head of fibula
        • great auricular nerve
    • Muscles
      • Paralysis
      • muscle wasting
    • Trophic ulcers

Diagnosis

  • Clinical examination
    • Examination of
      • skin
      • nerves
      • pain sensation
      • sweating
      • motor functions
      • nerve thickening
  • Laboratory Examination
    • Skin slit smears
      • Skin is slit without drawing blood
      • smear taken & stained for bacilli
        • usually from ear lobes
      • The quantity and the morphology is measured
    • Skin biopsy
      • of lesion edge/nerve
    • Mitsuda reaction (Not diagnostic)
      • Skin test with lepromin
        • made from autocalved Mycobacterium leprae
      • Granulomatous nodule after 28 days in tuberculoid and some boderline cases
      • Healthy persons may show a positive Mitsuda reaction
      • If no reaction –> lepromatous leprosy

Treatment

Multidrug therapy (MDT)

  • Combinations of
    • Rifampicin
      • urine slightly reddish for few hours
    • Clofazimine
      • brownish black discoloration
      • drness of skin
    • Dapsone
      • allergic reaction towards sulpha drugs
        • itchy skin rashes
        • exfoliative dermatitis
      • do not give to patients who are allergic
  • May develop drug resistance if only 1 drug used

_____________________________________________________________________

Reactions in leprosy

Non-Lepromatous lepra reaction (Type 1 lepra reaction)

  • Seen following treatment of boderline leprosy
    • Type 4 delayed hypersensitivity reaction
  • Last for few days to several weeks
  • Reactions
    • Acute inflammation of preexisting borderline lesion
    • Skin lesions become swollen and erythematous
    • Neurological lesions
      • ulnar nerve palsy may occur abruptly
    • Both upgrading or reversabile reaction
      • more tuberculoid or more lepromatous

Erythema Nodosum Leprosum (Type 2 lepra reaction)

    • Humeral antibody response to antigen antibody complex
      • type III hypersensitivity reaction
    • systemic manifestations
      • Fever
    • Athralgia
    • Painful subcutaneous erythematous nodules
    • Iritis

_____________________________________________________________________

Prevention & control of leprosy

  • Primary prevention
    • Health promotion
    • improve housing standards
    • standard of living
    • BCG (Limited protection)
  • Secondary prevention
    • Early diagnosis & treatment
    • WHO-Multi drug treatment
      • follow up 5 years,
      • Tuberculoid – 6 months
      • Borderline & lepromatous – 2 years
  • Tertiary prevention
    • Disability limitation
    • Care of the hands, feet, neuropathy and loss of sight
    • Rehabilitation
      • Restoration of function
      • Deformities, loss of limbs fingers, nose etc

_____________________________________________________________________

Poliomyelitis

image

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  • Definition
    • An acute viral infection
      • with severity ranging from inapparent infection to non-specific febrile illness, aseptic meningitis, paralytic disease and death
    • Minor illness includes (if the disease progresses)
      • fever
      • malaise
      • headache
      • nausea
      • vomiting
    • Severe illness includes
      • muscle pain
      • stiffness of neck
      • stiffness back with/without paralysis
    • The site of paralysis depends upon the location of the nerve cell destruction in the spinal cord/the brain stem
  • Infectious agent
    • Polio virus Type 1
      • Brunhilde
      • most commonly seen in epidemics
    • Type 2
      • Leon
    • Type 3
      • Lansing (genus Enterovirus)

Epidemiology

  • Occurrence
    • Worldwide
    • disease of children & adolescents
  • Reservoir
    • Man only
      • people with inapparent infections
  • Mode of transmission
    • Direct contact through close association
    • Rare instances – fecaloral route
  • Incubation period
    • 7-14 days of paralytic cases
    • Range 3-35 days

Susceptibility and resistance

  • Susceptibility to infection is general
  • paralytic infections are rare
  • Lifelong specific immunity
    • immunisation at birth
    • Infants born to immune mothers have transient passive immunity Injections of other vaccines may provoke paralysis
    • Second attacks are rare
      • due to different type of polio virus
  • Tonsillectomy increases the risk of bulbar involvement
  • Strenuous exercise is known to make the paralysis worse in the exercised limb
    • during the prodromal phase
  • Statistics
    • 90% have no or almost no symptoms/indistinguishable from influenza
    • 9% have non-paralytic polio
    • 1% have spinal/bulbar polio
      • 10% die
      • 50% recover fully
      • 40% are left with only partial recovery/permanent paralysis
    • 0.4% of permanent paralysis,
      • 1 or both lower limbs
    • 0.01%
      • Quadriplegia
      • respiratory paralysis

    Pathophysiology of polio

    • Polio is generalized infection
      • which may involve the whole body including muscles, liver spleen, and gastrointestinal system
    • Anterior horn cells are chiefly affected
      • Degeneration & loss of Nissls granules
        • uptil complete disappearance of the cells
      • This results in the lower motor neuron paralysis
        • with asymmetrical paralysis & normal sensation
        • Paralysis occurs in small proportion & may be minimal to severe
        • Paralysis may cause shortening & decrease diameter of the bones
      • Most common muscles involved
        • extensor of hips
        • extensor of knees
        • dorsiflesion of ankles
        • deltoid
        • triceps
        • thenar muscles
        • respiratory muscles
        • spinal muscles
    • Bulbar paralysis
      • Pharyngeal paralysis
        • inability to swallow food, drinks and own secretions
        • inability to cough and difficulty in speaking
    • Respiratory paralysis
      • Respiratory muscles rare
      • Intercostal muscles
        • Anterior horn cells of the thoracic region
      • Diaphragm
        • Anterior horn cells of mid cervical
    • Fibrillations of muscles
      • Paralyzed muscles show fine ripples of contractions

    Diagnosis of polio

    • Clinical examination
      • confirmation of sudden onset of acute flaccid paralysis (AFP)
        • with no loss of sensation
    • Laboratory culture (stool)
      • isolate virus
        • 100% isolation of virus within 2 weeks of onset
          • WHO criteria for certification of polio free
        • 50% within three weeks of onset
        • 25% within 6 weeks

    Prevention of polio

    • Primary prevention
      • Health education
      • Oral polio virus vaccine (OPV)
        • Live attenuated Sabin Vaccine
        • OPV given in Malaysia in
          • 2nd month
          • 3rd month
          • 5th month
        • Booster
          • 18 months
          • standard 1
      • Intramuscular injection
        • Salk Vaccine
    • Secondary Prevention
      • Early diagnosis and prevention
        • Spinal polio and bulbar polio
      • Disability limitation
        • avoid factors that potentiate paralysis
        • eg. operations, injections & strenuous exercise
      • Prevention of deformities & contractures (of bone?)
    • Tertiary prevention (Rehabilitation)
      • Surgery on contractures
      • equinus foot
      • wheel chair for the disabled

    Eradication of polio

    • Polio transmission is now  limited to about 9 countries
      • Afghanistan
      • Pakistan
      • India
      • Angola
      • Congo
      • Nigeria
      • Somalia
      • Ethiopia
      • Sudan
    • Eradication is possible because the virus affects only humans
      • no animal reservoir
      • no long term carriers
      • virus cannot survive outside the human body for long
    • Acute flaccid paralysis (AFP) is being carried out all countries that have declared free of polio
    • Malaysia is free of polio
  • Degeneration & regeneration of peripheral nerves

    5

    Peripheral nerve injuries

    image

    • Due to
      • Trauma
      • acute compression
    • Signs & symptoms
      • Loss of motor function
      • Loss of sensory function
    • Pathology
      • Demyelination/axonal degeneration
      • Disruption of the sensory/motor function of the injured nerve
      • Remyelination with axonal regeneration
      • Reinnervation of the sensory receptors & muscle end plates

    Degenerative changes

    • Axonal injury
      • Degenerative changes at proximal & distal end
        • Anterograde degeneration (Wallerian Degeneration)
          • Affecting the
            1. Injured neuron
            2. Neurons functionally connected to the injured neuron
          • Transneural degeneration
            • also degenerate neurons that synapses with the injured neuron
          • Starts in 24 hours
        • Retrograde Degeneration
          • Extends up to the first node of Ranvier proximal to the injury
          • Changes in the dendritic tree
            • the parent cell body & the part of the axon still attached to the cell body
          • Chromatolytic changes
          • Swelling of the cell
          • Displacement of the nucleus to periphery
            • sometimes extruded out
          • Fragmentation & reduction of Golgi apparatus
          • Disappearance of neurofibrils

    image

    Chromatolysis

    • disintegration of the Nissl substance
      • begins within 24 – 48 hours
      • begins near the axon hillock & spreads to other parts
    • occurs in certain infectious or degenerative diseases of the nervous system
      • poliomyelitis
      • progressive muscular atrophy
    • degree of chromatolysis depends on
      • proximity of the site of injury to the nerve cell
    • more in motor neurons

    Wallerian degeneration

    image

    Process that results when a nerve fibre is cut or crushed, in which the part of the axon separated from the neuron’s cell body degenerates.

    Pre-degeneration reactions – 1st things that happen when there is injury

    • Decentralisation of the nucleus
      • increased ribosomes surrounding the nucleus
    • Immune response
      • Macrophages start attacking the Schwann cells of the distal segment
    • Nervous system reaction
      • All adjacent neurons start extending sprouts of their axons
      • towards the injured neuron
    • Enzymatic Action
      • The axon of the distal segment is broken down by enzymes

    Pathophysiology

    image

    • Axonal degeneration
      • Axis cylinder (axolemma) swells & breaks up into small pieces
        • Enzymatic Action
          • The axon of the distal segment is broken down by enzymes
            • the products of this action is carried by retrograde transport to the soma
        • Debris appear in the space occupied by axis cylinder
      • Myelin sheath disintegrate into fat droplets
      • Neurilemmal sheath intact
    • Myelin clearance
      • Immune response
        • Macrophages start attacking the Schwann cells of the distal segment
        • Macrophages invade & remove the debris of axis cylinder
    • Regeneration ( begins about 20 days after injury)
      • Schwann cells multiply
        • Macrophages produce interleukin-1 which stimulates Schwann cells to secrete substances that promote nerve growth
        • forms a solid cord of elongated cells within the endoneural tube –> towards the target tissue
          • those that did not reach the target tissue will start dying
        • growth path for axon
      • Adjacent basal lamina separate
        • creating an annular compartment
      • Neurilemmal tube becomes empty
        • now filled by cytoplasm of Schwann cells
      • Axonal sprouts (neurofibrils)
        • Neurofibrils grow out in all directions from the proximal axon
        • Sprouts grows into the distal annular compartment
        • All but one axonal sprout degenerate
        • Surviving fibril enlarges to fill the distal tube Regenerated fiber rarely attains a fiber diameter more than 80% of normal
      • Schwann cell form myelin sheath around the reinnervating axonal sprout
        • Sheath begins to develop in about 15 days
        • Myelin sheath is completed in one year
      • Regeneration in the cell body
        • Nissl granules reappear
        • Golgi apparatus reappear
        • The cell regains its normal size
        • Nucleus returns to central position

    Summary:

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    Transneural degeneration

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  • Degeneration of the neuron with which the injured afferent nerve synapses
    • This neuron is not the one that is injured
  • Examples
    • Optic nerve injury leads to degeneration of the lateral geniculate body
    • Injury to posterior nerve root leading to degeneration of dorsal horn of spinal cord
  • Changes in nerve degeneration

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    • There will be neurogeneic rearrangement
      • the growing axon does not necessarily follow the expected growth path
      • incomplete nerve regeneration
    • Criteria for complete nerve regeneration
      • Gap between cut ends of neuron
        • should not be greater than 3mm
      • Neurilemma should be present
      • Nucleus must be intact
        • should not be extruded
      • Two cut ends should remain in the same line
        • or else there will be rearrangement
      • Nerve regeneration is generally limited
        • because axons become entangled in the area of tissue damage
      • Neurotropins
        • nerve growth factors – influence nerve regeneration
        • Growth factors produced by neurons, glial cells, Schwann cells, and target cells

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    Classification of nerve injuries

    Seddon’s classification (3 types)

    1. Neuropraxia
      • Caused by
        • minor nerve stretch/pressure
          • causing ischemic injury to the nerve
          • Results in conduction block
            • without any structural damage
      • Electrodiagnostic study
        • normal – above and below the level of injury
        • No denervation muscle changes are present
      • Recovery
        • Once remyelinated, complete recovery occurs
    2. Axonotemesis
      • Caused by
        • excessive stress injury to the nerve
      • Pathology
        • The basal lamina of Schwann cells & other sheaths are intact
        • The epineurium & other supporting structures are not disrupted
          • internal architecture is relatively well preserved
        • Cause Wallerian degeneration distal to the injury
        • Endoneural tubes remain intact
      • Electrodiagnostic studies
        • denervation changes in the affected muscles
      • Recovery
        • In cases of reinnervation
          • motor unit potentials (MUPs) are present
        • Once remyelinated
          • complete recovery with axons reinnervating their original motor and sensory targets
    3. Neurotemesis
      • Caused by
        • penetrating injury to the nerve
      • Pathology
        • All the sheaths are disrupted
        • Physical gaps in the nerve may occur even though an epineurial sheath appears in continuity – after traction or crush
      • Recovery
        • No recovery unless repair is undertaken
        • Unrepaired nerve will be completely replaced by fibrous tissue
          • there is complete loss of anatomic continuity

    Sunderland’s classification (6 degrees of nerve injury)

    1st degree (neuropraxia)
    • most common
    • caused by
      • pressure, occlusion of blood flow, hypoxia
    • mild demyelination occurs
      • without axonal damage
      • there is conduction block
    2nd degree (axonotemesis)
    • Caused by
      • severe prolonged pressure on the nerves
    • May cause Wallerian deneration
    • Repair & regeneration of nerve takes a long time
    3rd degree
    • Endoneurium interrupted
      • epineurium & perineurium intact
    • Incomplete recovery at 3 months
      • recovery slow
      • regeneration is incomplete
    4th degree
    • Endoneurium, epineurium & perineurium interrupted
    • No recovery at 3 months
      • requires surgery to restore neural continuity
      • regeneration is incomplete
    5th degree
    • Complete transaction of the nerve
    • Requires surgery to restore neural continuity
    6th degree
    • Mixed nerve injury
      • that combines other degrees of nerve injuries

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    Tinel sign

    • Light percussion on the nerve with a patellar hammer
      • from distal to the proximal end
    • A tingling sensation is experienced at the level of regeneration
      • As the regeneration of the axon grows, the level of tingling sensation also shifts
    • Absent in neuropraxia

    Denervation hypersensitivit
    y

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    • Following a section (cut) of a motor nerve
    • Pathology
      • A deficiency of chemical messenger (due to denervation) generally produces an up-regulation of its receptors
      • Acetyl choline receptors increase
        • more than 10 folds in number
        • dispersed over the entire surface of the sarcolemma
      • Sensitivity of the receptors towards acetylcholine increases
        • (desperate to be innervated)
    • Denervation also lowers the membrane potential
      • Muscles more prone to fibrillations
    • After regeneration
      • functional innervation of the muscle is reestablished and sensitivity to acetyl choline decreases
      • resting membrane potential is restored
        • fibrillation disappears after regeneration
    • Other muscles
      • Smooth muscle
        • does not atrophy when denervated
        • becomes hyperresponsive to the chemical mediator that normally activates it
      • Denervated exocrine glands [except sweat glands]
        • become hypersensitive
        • due to the synthesis or activation of more receptors
        • A deficiency of chemical messenger generally produces an up-regulation of its receptors
          • Lack of reuptake of secreted neurotransmitters because pre-synaptic nerve is not present
          • Therefore excess neurotransmitters in the ‘synaptic space’ –> hyperreactivity of muscles
      • Multiple sclerosis
        • Demyelination of oligodendrocytes in the central nervous system & Schwann cells in the peripheral nervous system
        • Disruption of connection between upper motor neurons & the lower motor neurons
        • Can cause
          • increased muscle tone
          • difficulty controlling muscles
          • exaggerated reflexes
          • muscle spasms