Peripheral Neuropathy Flashcards
what are the causes of nervous system injury?
hypoxia trauma toxic insult metabolic abnormalities nutritional deficiencies infections abnormalities - intrinsic, ageing
what are the two speeds of neuron damage?
rapid necrosis
slow atrophy
acute neuronal injury also is also known as…
red neuron
when does acute neuronal injury occur?
hypoxia/ischaemia
what are the microscopic features of acute neuronal injury?
- Shrinking and angulation of nuclei
- Loss of the nucleolus
- Intensely red cytoplasm
what are the electro toxicity affects in acute neuronal injury?
Glutamate and Oxygen free radical formation bringing about CALCIUM influx
what is the consequence of electrotoxicity in acute neuronal injury?
Calcium entry triggers: • Protease activation • Mitochondrial dysfunction • Oxidative stress • Apoptosis and Necrosis
what is the axonal reaction in nerve injury?
o Increased protein synthesis -> cell body swelling, enlarged nucleolus
o Chromatolysis – margination and loss of Nissl granules
o Degeneration of axon and myelin sheath distal to injury “Wallerian degeneration”
what are the features of simple neuronal atrophy?
o Shrunken o Angulated and lost neurons o small dark nuclei o lipofuscin pigment o reactive gliosis
what are subcellular neuronal alterations?
o Alterations to neuronal organelles and cytoskeleton
what are examples of subcellular alterations?
neurofibrillary tangles in Alzheimer’s disease
lewy bodies in lewy body dementia and Parkinsons
Viral infections
gliosis affects which type of neuronal cell?
astrocytes
what are the features of gliosis?
o Astrocyte hyperplasia and hypertrophy – grow in number and size
o Nucleus enlarges, becomes vesicular and the nucleolus is prominent
o Cytoplasmic expansion with extension of ramifying processes
what do old gliotic lesions look like?
nuclei become small and dark and lie in a dense net of processes
how do oligodendrocytes respond to damage?
limited reaction to injury - Less sensitive than neurones, due to having low anti-oxidant reserves and high intracellular iron
Oligodendrocytes damage is feature of which primary demyelinating diseases?
Multiple Sclerosis, Acute disseminated encephalomyelitis, Acute haemorrhagic leukoencephalitis
Oligodendrocytes damage is feature of which secondary demyelinating diseases?
Viral - Progressive multifocal leukoencephalopathy (PML)
Metabolic - E.g. central pontine myelinosis
Toxic - CO, organic solvents, cyanide
axonal loss in the CNS is generally….
irreversible
ependymal cells are effected in which pathological processes?
Infection and tumours
what is the process of microglia response?
- Microglia proliferate
- Recruited through inflammatory mediators
- Form aggregates around areas of necrotic and damaged tissues
- Seen aggregating and phagocytosing cell debris, removing dead and dying cellular material and taking on foamy cytoplasm
what is the role of M2 microglia?
anti-inflammatory, phagocytic, more acute
what is the role of M1 microglia?
pro-inflammatory, more chronic (important mediators of Alzhemiers and MS)
oedema in neuronal cells occurs due to
cytotoxic
ionic
vasogenic
haemorrhage conversion
how to cytotoxic processes lead to cellular oedema?
dying cells accumulate water because osmotically active extracellular ions such as Na+ and Cl- move into cells and take water with them
when does cytotoxic oedema occur?
intoxication, Reye’s and severe hypothermia
what are the causes of ionic oedema?
hyponatraemia and excess water intake e.g. SIADH
ionic oedema of neuron cells is the…
first dysfunction of the BBB
what is the process of ionic oedema?
o cytotoxic oedema, causes extracellular space to lack Na+
o Na ions cross the blood brain barrier (BBB), causing chloride ion transport = osmotic gradient
when does vasogenic oedema occur?
along with deterioration and breakdown in the BBB
what are the causes of vasogenic oedema?
trauma, tumours, inflammation and infection and hypertensive encephalopathy
what is the process of vasogenic oedema?
Disruption of endothelial tight junctions allows plasma proteins, such as albumin which are osmotic factors, cross into the extracellular space, and water follows
what is haemorrhagic conversion in neuronal injury?
o occurs when endothelial integrity is completely lost and blood can enter the extracellular space
what are the symptoms of peripheral neuropathy of large fibre motor nerves?
Weakness, Unsteadiness, wasting
what are the symptoms of peripheral neuropathy of large fibre sensory nerves?
Numbness
Paraesthesia
Unsteadiness
what are the symptoms of peripheral neuropathy of small fibre nerves?
Pain
Dysesthesia
what are the symptoms of peripheral neuropathy of autonomic nerves?
Dizziness (postural hypotension)
Impotence
Nausea and vomiting (gastroparesis)
how is power affected in peripheral neuropathy of large fibre motor nerves?
Reduced
how is power affected in peripheral neuropathy of large fibre sensory nerves?
Normal
how is power affected in peripheral neuropathy of small fibre nerves?
Normal
how is power affected in peripheral neuropathy of autonomic nerves?
Normal
how is sensation affected in peripheral neuropathy of large fibre motor nerves?
Normal
how is sensation affected in peripheral neuropathy of large fibre sensory nerves?
Vibration and JPS reduced
how is sensation affected in peripheral neuropathy of small fibre nerves?
Pin prick and temperature reduced
how is sensation affected in peripheral neuropathy of autonomic nerves?
Normal
how are reflexes affected in peripheral neuropathy of large fibre motor nerves?
Absent
how are reflexes affected in peripheral neuropathy of large fibre sensory nerves?
Absent
how are reflexes affected in peripheral neuropathy of small fibre nerves?
Present
how are reflexes affected in peripheral neuropathy of autonomic nerves?
Present
what are the patterns of loss in length dependent peripheral neuropathy?
- Glove and stocking
- Mild
- Moderate
- Severe
what are the different types of nerve damage based on location?
Radiculopathy
Plexopathy
Peripheral Neuropathy
what are the different types of peripheral neuropathy?
Mononeuropathy Mononeuritis Multiplex (length dependent) peripheral neuropathy
what is mononeuropathy?
neuropathy affecting a single nerve
what are the causes of mononeuropathy?
physical compression
direct injury to a nerve, ischemia, or inflammation
what is mononeuritis multiplex?
is simultaneous or sequential involvement of individual noncontiguous nerve trunks, either partially or completely, evolving over days to years
what is the pattern of involvement?
initally asymmetric but becomes more symmetrical
what are the clinical features of mononeuritis multiplex?
pain
muscle weakness and loss of reflexes
what are the causes of mononeuritis multiplex?
diabetes mellitus polyarteritis nodosa, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, rheumatoid arthritis, systemic lupus erythematosus (SLE), leprosy, lyme disease, Parvovirus B19, HIV, sarcoidosis, cryoglobulinemia,
what is radiculopathy?
mechanical compression of a nerve root, usually at the exit foramen or lateral recess
what are the causes of radiculopathy?
o degenerative disc disease, OA, facet joint degeneration/hypertrophy, ligamentous hypertrophy, spondylolisthesis
o rarer causes – radiation, DM, neoplastic disease, meningeal based disease
what are the clinical features of radiculopathy?
motor or sensory deficits, pain, weakness, numbness in distribution of nerve root
where does radiculopathy most commonly occur?
cervical spine C6-C8
what are the clinical features of plexopathy?
pain, loss of motor control and sensory deficits in regions supplied
what is plexopathy?
disorder affecting network of nerves, blood vessels or lymph vessels of the brachial or lumbosacral plexus
what are the causes of plexopathy?
o Primary – trauma
o Secondary – co morbid vascular disease, infection, idiopathic
what is autonomic neuropathy?
group of symptoms that occur when there is damage to the nerves that manage every day body functions
what are the causes of autonomic neuopathies?
o Chronic – diabetes, amyloidosis, hereditary
o Acute – GBS, porphyria
o Other – alcohol abuse, Guillain Barre, HIV/AIDs, MS< Parkinson, Spinal cord injury
what are the two ways in which nerves are damaged?
- Axonal loss
* Peripheral nerve demyelination
what are the causes of axonal loss?
o Idiopathic (age related) o Vasculitis* o Paraneoplastic o Infections o Drugs/Toxins o Metabolic
what are the vasculitis causes of axonal loss?
ANCA +ve, Rhematoid arthritis/Sjrogens syndrome (ANA/ENA +ve)
what are the paraneoplastic causes of axonal loss?
Myeloma, Antibody mediated (eg breast cancer/SCLC Anti hu/yo)
what are the infective causes of axonal loss?
HIV, Syphilis, Lyme*, Hepatis B/C (cryoglobulin mediated)
what are the drug/toxin causes of axonal loss?
Alcohol, Amiodarone, Phenytoin, Chemotherapy (cisplatin/vincristine)
what are the metabolic causes of axonal loss?
Diabetes, B12/folate deficiencies (other), Hypothyroidism, Chronic uremia, Porphyria
what is the conduction speed in axonal neuropathies?
near normal
what are the clinical symptoms of axonal neuropathies?
Movements of muscles effected
what are the clinical symptoms in demyelinating neuropathy?
Both sensory and motor nerves
what is the conduction speed in demyelinating neuropathy?
much slower
what are the acute causes of demyelinating neuropathy?
Guillaine Barre syndrome or AIDP
what are the chronic causes of demyelinating neuropathy?
- CIDP (chronic inflammatory demyelinating polyradiculopathy).
- Hereditary sensory motor neuropathy
what is the the treatment of axonal neuropathy?
- Treat cause (ie clear hepatitis C)
* Symptomatic treatment – physiotherapy, orthotics, neuropathic pain relief.
what is the the treatment of vasculitic axonal neuropathy?
• Pulsed IV methylprednisolone + cyclophosphamide
what is the management of demyelinating neuropathy?
- IVIg (pooled immunoglobulin from donors)
- Steroids
- Azathioprine, mycophenalate, cyclophosphamide
what type of neuropathy is GBS?
acute inflammatory demyelinating polyneuropathy
what is the pathophysiology of GBS?
• antibody and cell mediated reactions to peripheral nerve myelin are involved
which antibodies are involved in GBS?
antibodies to gangliosides – pure sensory GD1b, severe GD1a/GD1b or GD1b/GT1b
Also myelin glycoproteins
what is the immune process in GBS?
- perivascular infiltration with lymphocytes occurs within peripheral nerve and roots
- lymphocytes and macrophages release cytokines which damage Schwann cell/myelin
what is the disease progression in GBS?
• segmental demyelination results with secondary axonal damage if the process is severe
what are the causes of GBS?
infection immunisations antitoxins trauma surgery malignant disease and immunodeficiency
which infections are implicated in GBS?
o viral – cytomegalovirus Epstein Barr, varicella zoster, hep B, hep C, mumps
o bacterial – campylobacter jejuni, mycoplasma
what are the main clinical symptoms of GBS?
begins in lower extremities and ascends bilaterally
1. Weakness
2. Ataxia
3. Bilateral paraesthesia Progressing to Paralysis
Causes problem with - respiration, talking, swallowing, bowel and bladder funciton
what is the onset of GBS?
progresses over hours to days
severe GBS can lead to what involvement?
respiratory and bulbar involvement, also autonomic
what investigations are used in GBS diagnosis?
- nerve conduction studies
- LP
- LFTs
- spirometry
- antiganglioside antibody
what additional investigations are used in GBS diagnosis?
serology, stool culture, HIV antibodies, spinal MRI, Borrelia burgdorferi serology, CSF meningococcal polymerase chain reaction (PCR), CSF cytology, CSF angiotensin-converting enzyme (ACE), chest x-ray, CSF VDRL, CSF West Nile PCR
what is the management of GBS?
Plasma exchange
Supportive treatment
if without IgA Deficiency or renal failure: IV Immunoglobulin
what supportive management is used in GBS?
o pulse and BP monitoring
o DVT prophylaxis – heparin and support stockings
o intubation and ventilation
o pain in acute phase: gabapentin or carbamazepine
o Long term pain: Tricyclic antidepressants, tramadol, gabapentin, carbamazepine, or mexiletine
o rehabilitation
o hypotension – fluid boluses
