Pathology of Medical Disorders of Peripheral Nerves Flashcards
What must be considered when trying to understand what kind of peripheral nerve disorder a condition is?
Whether its UMN or LMN
Whether it affects motor or sensory neurons
The level of damage (anterior horn, peripheral nerve and where on the peripheral nerve, or is it at the level of the NMJ)
How can UMN and LMN sydromes be distinguished?
UMN results in spastic paralysis. LMN results in flaccid paralysis
UMN causes no atrophy, LMN causes atrophy
UMN increases deep tendon reflex, LMN results in absent deep tendon reflex
UMN causes positive babinski sign, LMN has no pathological reflexes.
Superficial reflexes are absent in UMN but present in LMN syndrome
UMN does not present with fasciculation and fibrillation whereas LMN could present with it.
What are the kinds of peripheral nerve disorders? What are some examples of these disorders?
A VITAMIN CDEP
Autoimmune (Guillan-Barre Synd)
Vascular (Vasculitis, amyloidosis)
Infective/inflammatory (Herpes zoster (shingles))
Traumatic/Toxic (alcohol)
Acquired
Metabolic (daibetes/uraemia)
Iatrogenic
Neurological, neoplastic, nutritional (vitamin deficiency)
Congenital (Charcot-marie-Tooth neuropathy)
Degenerative/drugs
Environmental/endocrine
Psychosomatic
What are the common patterns associated with peripheral nerve damage?
Polyneuropathy (symmetrical, distal-predominant)
Mononeuropathy (Single nerve damaged)
Mononeuritis multiplex
What most commonly causes polyneuropathy?
Toxic or metabolic causes of peripheral nerve damage.
What most commonly causes mononeuropathy?
Trauma, entrapment, and infection
What most commonly causes mononeuritis multiplex?
Vasculitis and amyloidosis
What is guillain-Barré syndrome?
A rapidly progressive, acte, demyelinating condition that affects motor axons and is caused by autoimmunity.
How rapidly does Guillain-Barre syndrome progress?
It is an ascending paralysis that causes respiratory muscle failure within days and reaches its maximum at 3 days.
What can trigger guillain Barre syndrome?
Infections from EBV CMV HIV Zika and campylobacter jejuni
What is damaged during Guillan-Barre syndrome?
Nerve roots and proximal nerve segments are damaged and inflamed resulting in Acute Inflammatory Demyelinating Polyneuropathy (AIDP)
What happens to CSF in Guillan-Barre syndrome?
Increase in protein
Cell counts are normal
Which neurons are affected by Guillan-Barre syndrome?
Motor neurons which are demyelinated
How is Guillan-Barre syndrome treated?
Plasmaphoresis to get antibodies out of the system.
Immunosuppression
How common is chronic inflammatory demyelinating polyneuropathy?
Most common acquired inflammatory peripheral neuropathy
What ages is chronic inflammatory demyelinating polyneuropathy most commonly seen in?
40 - 60 year olds
What is the most common cause of peripheral neuropathy?
Diabetes mellitus
What forms of neuropathy are common in diabetic patients?
Distal symmetrical sensorimotor polyneuropathy:
Asymmetrical diabetic neuropathies
Autonomic neuropathy
What common neuropathy damage is associated with asymmetrical diabetic neuropathies?
Thighs and proximal legs see muscle wasting due to damage to the lumbosacral plexus.
Mononeuropathies are also common
What signs indicate autonomic neuropathy?
Orthostatic hypotension
Erectile dysfunction
Gastroporesis
What happens during diabetic peripheral neuropathy?
Degeneration of axons, concentric basal lamina thickening of blood vessels (, possible demyelination and remyelination with schwann cell hypertrophy, and perivascular inflammation
What is gastroporesis?
Slow gastric emptying resulting in nausea and vomiting.
What is myasthenia gravis?
Autoantibodies that bind to AChR which results in fewer binding sites for acetylcholine resulting in weak signal transduction resulting in fatigue.
What kind of structures can be targeted by AChR autoantibodies?
Autoantibodies can potentially bind to:
Acetylcholine receptors (most commonly)
Muscle specific kinases (MuSK)
Lipoprotein like protein (Lrp4)
No need to know all of them just know that there are many sites of action rather than just the single AChR
What is the result of varying specificity of antibodies to AChR?
The sites they act on differ.
What kind of tumours cause antibody production against AChR?
Tumours of the thymus.
How is myasthenia gravis diagnosed?
Antibody titres, CT of the chest, EMG, nerve stimulation
How is myathenia gravis treated?
Cholinesterase inhibitors (pyridostigmine), plasmapheresis, thymectomy (if caused by thymus tumours)
What is lambert-Eaton syndrome most commonly caused by?
It is a paraneoplastic syndrome (most commonly associated with small cell lung carcinoma) that causes production of circulating antibodies that target the calcium channels at the NMJ.
How is Lambert-Eaton syndrome distinguished from Myasthenia Gravis syndrome?
Weakness is improved by repeated stimulation of muscles.
How is Lambert-Eaton syndrome treated?
Reducing titre of causative antibodies:
Plasmapharesis, IVIG, and immunosuppression
How do patients present if their problem is muscle related?
Weakness, atrophy, pseudohypertrophy, pain/altered sensation, failure of relaxation, fasciculations, and cramps
What should be investigated for muscle related illness?
Family history
Distribution of the weakness, atrophy, and pain.
Creating Kinase, EMG, Nerve Stimulation Studies
Imagine (MRI, Ultrasound)
Muscle biopsy/nerve biopsy
Genetic investigations
What are the common causes of neurogenic muscular disorders?
Peripheral neuropathies are most common.
Motor neurone disease
Spinal muscular atrophy
Polyneuropathy
What are common causes of myopathic muscular disorders?
Muscular dystrophies
Mitochondrial disorders
Myositis
Metabolic myopathies (lipid myopathies, glycogen storage disorders)
What are common causes of myopathic muscular disorders?
Muscular dystrophies
Mitochondrial disorders
Myositis
Metabolic myopathies (lipid myopathies, glycogen storage disorders)
What happens in motor neurone disease?
Degeneration of motor neurones in motor cortex of the brain (UMN clinical) or anterior horn of spinal cord (LMN clinical)
What are the subtypes of motor neurone disease and which nuclei/neurons are affected?
Amyotrophic lateral sclerosis (ALS) - corticospinal tracts
Progressive bulbar palsy (PBP) [hypoglossal nucleus]
Primary lateral sclerosis (PLS) Motor cortex brain (UMN)
Progressive muscular atrophy (PMA) anterior horn cells (LMN)
What are the common symptoms associated with motor neurone disease?
Weakness
Muscle atrophy
Fasciculations
Could present with difficulty swallowing and involvement of respiratory muscles
What causes motor neurone disease?
It is mostly idiopathic/sporadic
10% of cases are hereditary due to autosomal dominant mutations
What dementia is associated with amyotrophic lateral sclerosis?
Frontotemporal lobar degeneration/frontotemporal dementia
What is the difference between muscular dystrophies and congenital muscular dystrophies?
Muscular dystrophies are progressive but start off with normal muscular function at birth. (eg limb girdle muscular dystrophy)
Congenital muscular dystrophies are progressive but the onset is much earlier (eg duchenne’s muscular dystrophy)
What are congenital myopathies?
Static muscle defects (floppy muscles) and these defects can potentially show some improvement over time.
When do congenital myopathies present?
In infancy
What kind of muscle disorders is central core disease?
Congenital myopathy
How is duchenne’s muscular dystrophy inherited?
It is X-linked recessive
How many people have duchenne’s muscular dystrophy?
1/3500 male births
What kind of muscle does duchenne’s muscular dystrophy affect and what is the prognosis like?
Cardiac + skeletal muscle including respiratory muscles. Prognosis as a result is not very good. It is invariably fatal.
How does duchenne’s muscular dystrophy present in clinic?
Clumsiness, shoulder and pelvic girdle weakness.
Pseudohypertrophy of calves, toe walking, hyperlordosis
Heart failure and arrhythmia
Variable cognitive impairment.
What factors does severity of duchenne’s muscular dystropy depend on?
The extent of dystrophin deficiency.
What causes the symptoms of duchenne’s muscular dystrophy?
Myofibers encounter necrosis, regeneration, and fibrosis due to muscles pulling themselves apart and damaging the membrane.
How is duchenne’s muscular dystrophy detected?
Immunohistochemical stains, absence of dystrophin protein staining of the muscle membrane.
Molecular pathology testing for dystrophin gene abnormality.
How does becker’s muscular dystrophy present?
In adulthood as a less severe condition (condition also presents later in life)
What is the difference between mutation in DMD and BMD?
Duchenne’s MD is out of frame.
Becker’s MD is an in-frame mutation
What are ion channel myopathies?
Inherited defects of ion channels in muscle fibers
What is malignant hyperthermia caused by?
RYRI mutation resulting in hyperexcitability
What kind of agents cause tetanic contractions in people with malignant hyperthermia?
Anaesthetic exposure.
What issues arise with anaesthetic use in people with malignant hyperthermia?
Excessive heat production and elevated CO2 production.
Tetanic contractions
How is malignant hyperthermia treated?
Dantrolene
Medical alert bracelet
Alternative anaesthetic agent is used if possible
What are metabolic myopathies?
Myopathies caused by errors in metabolism.
What are the symptoms of metabolic myopathies?
Manifestations vary with the kind of muscles involved.
Symptoms can be cardiac or neurological.
Rhobdomyolysis (often exercise-induced) severe pain in the muscle.
Myoglobinuria
How can glycogenoses be diagnosed?
Increased glycogen within skeletal muscle (can be visualised on special stains) and on electron microscopy.
Biochemical and molecular analysis can be done as is the case with metabolic myopathies
How can lipidoses be diagnosed?
Increased lipid droplets within skeletal muscles can be visualised on special stains (Oil Red O) and on electron microscopy.
Biochemical and molecular analysis can be done as is the case with metabolic myopathies
What is polymyositis?
An autoimmune disorder caused by increased MHCI expression on myofibers.
An elevated level of cytotoxic T cells, myofiber necrosis and regeneration results.
How is polymyositis diagnosed?
Muscle pain, weakness, elevated CK
How is polymyositis treated?
Corticosteroids and immunosuppression
What is dermatomyositis?
An inflammatory condition affecting skin and muscles
What causes dermatomyositis?
Almost always associated with malignancy.
What are the symptoms of dermatomyositis?
Cutaneous symptoms include gottron’s papules and a heliotrope rash.
Myopathic symptoms include pain, weakness, raised CK, and inflammatory markers
Pulmonary symptoms include interstitial lung disease
What is a heliotrope rash?
An erythematous rash on eyelids and upper cheek.
What are gottron’s papules?
Papules that appear on posterior surface of the hand and fingers (around nails)
What causes damage to fascicles in dermatomyositis?
MAC of complement pathway attacks endothelium of capillaries forcing them to close off and cause ischaemic damage to surrounding tissues
What is the most common inflammatory myopathy in people older than 60 years?
Inclusion body myositis
What are the clinical presentations of body myositis?
Weakness in proximal lower limb and distal upper limb (particularly long finger flexors)
What causes inclusion body myositis?
It is not fully understood but is thought to be immune mediated
What is the most common type of toxic myopathy?
Ethanol myopathy
What are the types of ethanol myopathy?
Acute and chronic
What is a common problem associated with acute ethanol myopathy?
After an episode of binge drinking, rhabdomyolysis, may lead to secondary renal failure.
What are the symptoms of acute ethanol myopathy?
Myocyte swelling
Necrosis
Regeneration
What are the symptoms of ethanol myopathy?
Type 2 fiber atrophy
What causes statin myopathy?
Either due to direct drug toxicity or immune mediated due to antiHMG-CoA reductase antibodies
What are mitochondrial myopathies?
Heterogenous groups of disorders with defects in oxidative phosphorylation.
What are the signs and symptoms of external opthalmoplegia (a mitochondrial myopathy)?
Proximal muscle weakness, ocular muscle involvement
What are the signs and symptoms common to many mitochondrial myopathies?
lactic acidosis, peripheral neuropathy, and cardiomyopathy may also result from mitochondrial myopathies
How are mitochondrial myopathies inherited?
Maternally
How are mitochondrial myopathies diagnosed?
Light microscope shows ragged red fibers, abnormalities on oxidative enzyme stains.
EM shows structural abnormalities
Respiratory chain enzyme complex assays can be conducted
Mitochondrial DNA testing
