Disorders of the NMJ Flashcards
UMN
- where are they
- clinical signs of lesions
glutamate is the major neruotransmitter between an UMN and a LMN
UMN: upper motor neruons
- first order neruons originating in the brain cortex or brainstem
- responsible for traveling down to the SC level and snypasing on the LMN there
UMN Lesions
- hyperreflexia and spacticity signs
- + babinski sign
- weakness: UE in the extensors and abductors more than flexors
- weakness: LE in the flexors more than the extensors
- weakness: facial weakness in lower 1/2 ; difficult to make facial expressions
LMN
- where are they
- clinical signs of lesion
LMN: lower motor meuron
- 2nd order neruons which come from the anterior gray column, nerve roots, crainal nerve nuclei
LMN Lesion
- fasiculations
- muslce wasting this can be a dramatic presentation
- weakness: dependent on the nerve root stuructre involved (either the anterior horn cell, spinal nerve roor or the peripheral nerve)
- weakness: facial invovlment= inability to move upper and lower face will all movements
Briefly: describe the NMJ
- alpha motor neruons axon termials recieve the action potential that has been propigated down the axon: they release acetylcholine into the cleft
- Ach bins to nicotonic receptors on the muscle cell
- this binding of post-synaptic nicotinic receptors causes an influx of Na+ and K+ = end-plate potential
- when the EPP reaches a votlage threshold, it propigates an AP to be released through the muscle cell & allow for muscular contration to occur
Approach to the pt. with muscle weakness
- have them define weakness: decreased strength or numbenss, clunsiness, pain, etc.
- preform a motor exam bilaterally, upper lower and trunk adn score 0-5; 5 = normal
- differentiate muscle dependent v pain-dependent weakness (ex. ankle sprain, it hurts to put weight, pain dependent weakness)
- then order appropriate labs as needed (EMG, NCS)
Brain Lesions & Weakness
if the weakness is secondary to a brain lesion;the following may be the common presentation
if its a cortical issue (UMN) , the weakness will present on the contralateral side as the brain lesion
- the LE and trunk will be weak if it is a medial issue, the UE and face will be weak if it is a lateral issue (deep issue? can see all areas weak)
there will be assocaited cognitive issues and CN signs usually with an UMN lesion this high
a lesion ofthe pons will result in ipsilateral face weakness and contralateral body weakness
Spinal Pathology & Weakness
if the weakness is a result of a spinal pathology the following may occur
- either the weakness is due to an anterior horn injury at the SC level –> weakness will be of the mucles involved (may mimic a radiculopathy)
- or the weakness at a SC level is impacting the lower leverls
Assocaited Symptoms with spine pathology weakness
- sensory findings below the SC lesion level
- can have UMN lesion signs below: since these are cut on their way down to target: hyperreflexia, babinski and bladder/bowel incontience
lesions above T6: may result in autonomic dysreflexia: since the nerves above T6 carry most of the autonomic function
- think bradycardia, flushing, HA etc.
may need MRI or LP
Plexopathies & Associated Weakness
if it is a plexopahty: there can be multiple muscles within a limb that are weak, and they will not follow a typical peripheral nerve pattern
- think brachial, lumbar and sacral plexuses
- will have decreased reflexes & assocaited sensory findings across more than 1 sensory nerve distribution
Peripheral Nerve Disorders & Assoicated Weakness
an injury will lead to issues with a specifc muscle that is innervated by that nerve, sparing other muscles in the area
Mononeuropathy: single nerve injury
Mononeurpathy multiplex: multiple single nerves in differnt locations (Lyme: think like one in the arm, one in the leg)
polyneuropahty: think multiple nerves within the same area (diabetic neuropathy: the entire leg/foot)
NMJ & Associated Weakness
- the weakness pattern will vary, usually it will be of the proximal muscles
Face?: extraoccular and bulbar muscles
Signs
- variability in time (hour to hour cahnges, better in the AM, worse at teh end of the day after activity)
- no sensory signs : since it is impacting the NMJ only
- +/- autonomic signs
Labs: EMG or NCS
always check for myasthenia gravic or lambert-eaton mysetheic syndrome
Weakness & Muscular Disorders
the weakness will be in…
- proximal muscles, BILATERALLY usually
- distal muscles affected later in disease progression
signs
- associated pain if its inflammatory
- no sensory issues; since its a mucls issue not nerves
- reflexes preserve
Myasthenia Gravis
Etiology
Pathology
Etiology
- a type 2 immune mediated disease : where antibodies cause functional damage
- the antibodies directly attack post-synaptic nicotnic Ach receptors –> thus decreasing the ability for a nerve impulse to be generated and an AP to occur + futher contraction
- most common disorder of the NMJ
- 20s-30s or late presentatino: commonly a thymoma
Pathology
- the antibody directly acts against the post-synaptic receptor that shouold bind to Ach, the attack leads the body to internalize the receptors; with less receptora avaible on the surface to uptake Ach
- distored motor endplate, lack of folds and reduced concentration of receptors
- the Ach is released fine, but the problem is there isnt enough receptors to bind to potentiate an AP
Antibodies: nAChR Ab (MC) or the muscle specific kinase ab (MuSK Ab)
Myasthenia Gravis
Symptoms
PE
Comorbid Conditions
Symptoms
- fatiguable weakness (worse at end of day or with activity)
- common ocular involvement: ptosis and diplopida (no impact of the pupil)
- Bublar muscle weakness: dyarthria or dysphagia
- Limb Weakness: proximal weakness (upper arms and upper legs) bilaterally and symmetric
- need to be cautious of respiratory muscles and breathing issues!!
PE
- altered gaze
- weakness with sustained activity
Comorbidites (since this is autoimmune, other autoimmune)
- hyperthyroidism (Graves)
- RA
- Scleroderma
- SLE
Myasthenia Gravis: Triggers for onset of diease or for exacerbation of disease
Most common Triggers
- Pregnancy
- Surgery
- Trauam
- Febrile Illness
- Drugs (lots)
Myasthenia Gravis
Diagnosis
Treatment
Diagnosis
- can be made clinically with symptoms and history
Tests
- Tensilon Test: when given tensilon: med that is anticholesterase, should increase muscle strength once given in MG pt.
- Antibody Testing: after Tensilon : nAChR then MuSK
- single fiber EMG is MOST SENSITIVE
- Chest CT for thymoma dx.
Treatment
- Pyridostigmine: an antiacetylchoninnesterase : this will help to decread degradation of the ACh in the synpase to allow more time to bind to receptors (no Ab effecT)
- immune mod. therapy: steroids, cyclosporines, azathioprine, plasmaphoresis
- if thymoma: thymectomy
Myasthenic Crisis
what is it
how to dx.
how to treat
What
- a MEDICAL EMERGENCY
- there is respiratory muscle weakness causing a failure to properly oxygenate and leading to respiratory failure
Triggers of Crisis
- Medications (lots)
- infections
- thymectomy
- pregnant
- tapering immunotherapeduic medications can bring this about
Dx.
- poor stats (O2, vitials)
- may or may not see accessory muscle use: since they’re so weak to begin with
- all pts. need a PFT
Treatmnet
- admit to ICU
- intubate/vent if needed
- plasmathersis or IVIG AND high dose steroids
