Neuro III (b) Flashcards
the 2 types of peripheral Nerve injury
1) Axonal injuries
2) Demyelinating Neuropathies
Morphological hallamrk in Axonal Neuropathies
Decrease in axons’ density –> Decrease in the strength of amplitude of nerve impulses
Morphological Hallmark in Demyelinating Neuropathies
Relative normal density of axons and signs of segmental demyelination and repair (remyelination) (axons with thin myelin sheaths and short internodes)
patho of Axonal Neuropathies
Direct injury to the axon –> Degeneration of the entire distal portion of the axon –> Secondary myelin loss (Wallerian degeneration)
Patho of Demyelinating Neuropathies
Damage to Schwann cells or myelin, but relative axonal sparing –> Occurrence of demyelination in individual myelin internodes (Segmental demyelination)
CM of Polyneuropathies
* peripheral nerve injury
Loss of sensation and paraesthesias (“stocking and glove” distribution -> Starts in the toes -> Spreads upward to the knees -> Lastly involves the hands)
* paraesthesias –> tingiling
3 types of Peripjeral nerve injury
1) Polyneuropathies (most common)
2) Poluneruritis Multiples
3) Mononeuropathy (involves a single nerver due to trauma or entrapment)
A mononeuropathy Syndrom
* peripheral nerve injury (single nerve)
Carpal Tunnel Syndrom
(compression of the median nerve)
cause of Gullain-Barre Syndrome
* Rapidly progressive acute demyelinating disorder
1) Infection (e.g. CMV, EBV, HIV, etc.) or vaccine –> Break down of self-tolerance –> Autoimmune response
2) Involvement of both humoral and cellular immune responses
Morphological featurs of Gullian-Barre Syndrome
Injury most extensive in the nerve roots and proximal nerve segments
CM of Gullian-Barre Syndrome
1) Parethesias (in the hands and feet)
2) Difficulty breathing (due to severe respiratory muscle weakness)
3) Absent or depressed deep tendon relfexes (paralysis)
4) Muscle weakness (begining in the legs and ascends)
CM of Chronic inflammatory Demyelinating polyneuropathy
1) Difficulty in walking
2) Weakness
3) Numbness
4) Pain or tingling sensations
Microscopic Findings:
* Peripheral nerves with segments of demyelination and remyelination
features of?
Chronic inflammatory demyelinating polyneuropathy
the most common peripheral neuropathy
Diabetic peripheral neuropathy
* px w/ long-standing DM
Risk factors of Diabetic Peripheral neuropathy
1) Microvascular changes (retinopathy, neuropathy, Nephropathy)
2) Hyperglycaemia
3) Accumulation of Glycosylated end products (HbA1c)
4) Changes in axonal metabolism
5) increased leveles of ROS
Type of Diabetic Neuropathies
1) Autonomic Neuropathy: Changes in bowel, cardiac or sexual function
2) Lumbosacral Radiculopathy: Lower extremity weakness and muscle atrophy
3) Distal Symmetric Sensorimotor Polyneuropathy: Paraesthesias and numbness
prognosis of Chronic inflammatory demylinating polyneuropathy
Complete recovery (some patients) but Recurrent bouts of symptomatic disease –> Permanent loss of nerve function (most common)
Toxic Form of Peripheral Neuropathy: Most susceptible <> —————–, Most pronounced <> ————–
Most susceptible –> Longest axons; Most pronounced –> Distal extremities
Examples of Systemic Vasculitides
Polyarteritis nodosa, Churg-Strauss Sy., Wegener granulomatosis
Most common clinical picture of Systemic Vasculitides
Mononeuritis multiplex (painful asymmetric mixed sensory and motor peripheral neuropathy)
Inherited Form of Peripheral Neuropathy: Most common cause –> Mutations in the ——— gene
PMP22 gene
Epi of Myasthenia Gravis
- More common in females
- Thymic hyperplasia (reactive hyperplasia of intra-thymic B cells) –> About 60% of patients
- Thymoma –> 20% of patients
cause/ patho of Myasthenia Gravis
Auto-Antibodies blocking the function of Acetylocholine receptors at motor end-plates –> Degradation and depletion of the receptors
CM of Myasthenia Gravis
Ptosis (droping eyelids) or Diplopia (double vision), due to weakness in the extra-ocular muscles
causes of Lambert-Eaton Syndrome
Auto-Antibodies inhibiting the function of pre-synaptic Calcium channels -> Reduction of Acetylocholine release into the synaptic cleft
CM of Lambert-Eaton Syndrome
Paraneoplastic Syndrome in patients with Small Cell Lung Carcinoma (SCLC)
Epi of Schwannomas (Neurilemmomas)
- bening
- Sporadic (most common); 10% associated with familial NF2
loc of Schwannomas
- Soft tissues
- Internal organs
- Spinal nerve roots
- Cranial nerves (Vestibular portion of the 8th nerve
Macroscopic Features:
* Circumscribed masses next to a nerve
* Globualr enlargment of a fascicle
* Yellow colouration of the cut surface, due to lipid accumulation
Microscopic Findings:
* Alternating areas of dense (“Antoni A”) and loose (“Antoni B”) texture
* **“Antoni A” **areas: Bland spindle cells arranged into intersecting fascicles
* “Verocay bodies”: Structures composed of alternating bands of nuclear palisading and anuclear strands between them
* Thick-walled hyalinised vessels
* Possible, presence of haemorrhage or cystic changes
features of?
Shwannomas (Neurilemmomas)
caues of Neurofibromatois Type 2
Loss of function mutation of the NF2 gene affecting Merlin (Schwannomin) protein
CF of NF2
Bilateral vestibular Schwannomas -> Hallmark of Neurofibromatosis Type 2
Hallmark of Neurofibromatosis Type 2?
Bilateral vestibular Schwannomas
———— : Familial condition associated with multiple Schwannomas, Ass. w/ the Absence of vestibular Schwannomas
Schwannomatosis
Microscopic Findings:
* Non-encapsulated tumours
* Haphazard cellular growth pattern
* Admixture of Schwann cells w wavy nuclei, mast cells, fibroblast-like cells and perineurial-like cells
* Background stroma: Loose wavy or dense collagen bundles or even myxoid consistency
features of?
Neurofibromatosis Type 2
localized Cutaneous Neurofibromas can exist as?
- solitary lesions or multiple in the context of NF1
- Superficial nodular or polypoid masses
Pathogonomic (symptom/sign) of NF1
Plexiform Neurofibromas
Microscopic Findings:
* Presence of residual axons found among the neoplastic cells
* Proliferation of schwann cells and fibroblasts
* Enlargement of the nerve
* Intact perineurium
* Classic “bag of worms appearance”
features of?
Plexifrom Neurofibromas
Diffuse Neurofibromas are ass w/?
NF1
Microscopic findings:
* Extensive infiltration of the dermis and subcutis
* Subcuataneous masses
* Marked expansion of dermal tissue
features of?
Diffuse Neurofibromas
Neurofibromatosis Type 1 is AKA?
Von Recklinghausen disease
Genetic predisposition of NF1
AD ; Mutations in the tumour suppressor gene Neurofibromin
CM of NF1
1) Learning disabilities
2) Seizures
3) Skeletal abnormalities (e.g. scoliosis)
4) Vascular abnormalities with arterial stenoses
5) Pigmented nodules of the iris (Lisch nodules)
6) Pigmented skin lesions (axillary freckling and café au lait spots)
7) Optic Glioma
8) Neurofibromas
9) Bone defects
who is likely to develop Malignant Peripheral Nerve Sheath tumours?
NF1 px
patho of Malignant Peripjeral nerve Sheat tumours
May originate from transformation of a Neurofibroma, usually of the plexiform type
cause of Traumatic Neuroma
Previous injury of a peripheral nerve
patho of Traumatic Neuroma
- Transection (divides) of axon –> Activation of regeneration mechanism –> Sprouting and elongation of processes (from the proximal axonal stump)
- Severe injury –> Disruption of the peri-neurial sheath –> Failure of proximal end to “meet” the distal end of the transected nerve –> Induction of a Schwann cell proliferation –> Development of a haphazard mixture of axons, Schwan cells and connective tissues
Occular Disroders
1) Conjunctivitis
2) Retinopathy of prematurity
3) Retinitis Pigmentosa
4) Diabetic Retinopathy
5) Senile Macular Degeneration
6) Glaucoma
7) Retinoblastoma
Cause of Conjuctivitis
Adenovirus (most common), bacteria
Prgnosis of Retinopathy of Prematurity
Blindness
casue of Retionopathy of prematurity
Toxicity of oxygen, administered because of NRDS (Newborn respiratory distress syndrome)
CM of Retinitis Pigmentosa
1) Retinal pigmentation
2) Peripheral vision loss (“Tunnel vision”) and progressive loss of Central Vision
cause of Diabetic Retinopathy
1) Non-proliferative:
- Micro-aneurysms, haemorrhages, soft (cotton-wool) exudates (micro-infarcts) and hard exudates (protein from damaged capillaries)
2) Proliferative:
- Neo-vascularisation and fibrosis
- Possible progression to haemorrhage and retinal detachment
patho of Senile Macular Degenration
Loss of central vision and pigmentary changes or haemorrhage in the macula
patho/CM of Open Angle Galucoma
1) Open Angle Glaucoma: Gradually increasing intraocular pressure –> Visual impairment –> Blindness
patho/CM of Angle-Closure Galucoma
Angle-Closure Glaucoma:
* Narrow anterior chamber angle
* Increase in intraocular pressure on dilatation of pupil
symptoms of open angle Glaucoma
1) Gradual loss of peripheral (side to side & up/down) visions, usually in both eyes
2) Tunnel vission
Smptoms of Closed angle Glaucoma
1) sudden,sever blurred vision
2) Severe pain- often affecting one eye at a time
Risk factors of Glaucoma
1) increased eye pressure
2) High bp
3) Family history of Glaucoma
4) >60 yrs
Gentic predispostion of Retinoblastoma
Homozygous deletion of Rb gene
Explain the “two hit” hypothesis of tumour development in Retinoblastoma
1) First “hit”: Inherited deletion in germ cells (familial cases) or somatic mutation (sporadic cases)
2) Second “hit”: Somatic mutation (both familial and sporadic cases)
Signs of Retinoblastoma
1) swollen eyes
2) shrunken eyes
3) A red, sore or swollen eye w/o infection
4) A white refelction in the pupil
Microscopic features:
- Multiple foci of necrosis
- Numerous apoptotic cells
- True rosette
- scant cytoplasm
- Flexner-Wintersteiner rosette
- Round to oval nuceli and finely granualr chromattin
features of?
Retinoblastoma
