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
Myasthenia Gravis
- thymoma population
- special surgical considerations
Thymoma population
- older pts 40+
- early onset idease with hyperplasia in the thymus
- presentin most nAChR ab + pt, rare in the MuSK+ pt.
Surgery
- anyone with MG getting surgery should be careful: prolonged paralysis can cause a crisis
- avoid inhaled anesthetics: try for neuraxial anesthisia
- do NOT use depolarizing paralytics
Botulism
Etiology
etiology
- illnesss due to neurotoxin produced by clostridum botulium
- sporm forming = heat resistant
- the spore: cleaves a specific vessel docking protein at NMJ blocking release of ACh
- can be from food (canned goods)
- wounds
- infant intestinal botulism
- inhalaition (biotterrorism)
Symptoms
- 12-36 hours after ingestion
- first sign: dipolpia and loss of accomidation
- normal sensroy exam
- dry mouth, dysphagia and dysphonia
- N/V
- floppy baby syndrome: loss of tone
Botulism
Diagnosis
Treament
Diagnosis
- identify toxin in serum or food source
reportable disease
Treatment
- antitoxin delivery (within 24 hours)
- respiratoy support
- fluids
ALS: Amyotrophic Lateral Sclerosis
Etiology
Symptoms
ALS Etiology
- a progressive damange to the spinal cord
- loss of muscle, effecting the corticospinal tract resulting in abnormal rigidity/hardening
- can progress to fronto-temporal dementai
- unknown cause, but can be familial
Symptoms
- weakness in LE, hands
- muscle cramps
- fasiculations in arms, sholders and tongue
- difficulty walking/ALDS or holding upright posture
- tripping/falling
PE Findings
- UMN and LMN lesions
- LMN: weakness, hypotonia/reflexia
- UMN: loss of fine motor deterity, spacticity, babinski, hyperreflexia
- dysarthria
- pseudobulbar effects (behavior, exact opposite)
- frontal lobe dysfunction
- respiratory dysfunction late in life
- preservation of occular movements, sensation and bowel/bladder function = since this is a motor issue
ALS
Diagnosis
Treatment
Diagnosis: mainly to rule out all other mimckers and other dx.
- NCS and EMGs
- get vit B12
- thyroid
- PTH
- HIV
- SPEP
- DNA studies form atrophy of spinal and bulobspinal issues
- urine for heavy metals
- barium swallow for aspiration assessment
treatment
- multidiscipinary : neurology referral
- Glutamate antagonists: can prolong the progression of the disease (if no respiratory effects yet)
- baclofen or clononzepam for spacticity (UMN)
- sertraline for pseduobulbar affects
- dysfunction based treatment
Muscualr Dytrophies
Etiology: Types
symptoms
Etiology
- a group of geentic disorders which show on muscle biopsy dystrophic changes (fiber splitting, increase connective tissue and less muscle)
- X-linked recessive disorders: Duchenne Muscular Dystrophy or Becker Muscular Dystrophy (DMD worse)
DMD
- most common; x-linked mutation in dystrphin gene (men only get it then)
- 3-5 years is age of onset
- severe symptoms and rapid progression
BMD
- less common and severe
- earyl teens/late childhod developemetn
- slower progression
Symptoms
- proximal arm and leg weakness
- pseudohypertrophy of calf (just increased connective tissue)
- dekayed motor milestones
- progressive muscle weakness (to impact cardiac and pulm. functions)
- Grower’s Sign: cant stnad up right
Muscualr Dystrophy
Diagnosis
Diagnosis
- marked elevation in ceratine kinsae
- genetic testing
- muscle biopsy to confirm
Treatment
- Prednisone to prolong ambulation and improve motor function (watchh long term effects)
- chronic thearpy : wathc cardiopulm and join contractures
- multiple disipline team to treat
Myotonic Dystrophy
Etiology
Symptoms
Diagnosis
Treatment
Etiology
- autosomoal dom. msucalr dystrophy: DM-I or DMII gener)
- causes weakness or atrophy
Symptoms
- weakness and atrophy of muscles
- prolong contraction of muscles (myotonia)
- inability to relax specific muslces after using them
- cataracts, cardiac issues, infertility in men androgenic alopecia
Diagnosis
- genetic testing
Treatment
- Mexilitine can help
- multidisc. team
Guillian Barre Syndrome
Etiology
Symptoms
Etiology
- acute mediated polyradiculopathy with motor involvement
- acute flaccid paralysis
- many types: acute inflamamtory demyleinating polyneuroapthy is mc
Risk Factors
- Viral infections (any)
- Bacterial Infections (camplybacter or mycoplasma)
- hodkins lymphoma
- immunizations (RARE)
Symptoms occur in acedning pattern from proximal to disal so legs proximal, arms prox, then legs distal, arms distal
- weakness
- sensory sx. stocking glove pattern
- depressed reflexes (or lost)
- pain (because of nerve root compression)
- autonomic abnormalities
- respiratory insuff.
- fascial or occular paresis
these usually occur over 4 weeks, then get better
GBS
Diagnosis
Treatmetn
Diagnosis
- CBC: could should leukocytosiswith left shift
- electrolytes: norm but r/o metabolic issue
- LP: could be normal at first 1-2 weeks then after 2 weeks see elevate CSF protein with minimal PMNs: high albumin and low PMNs
Treatment
- monitor respiraotry, clear secretions
- pressure ulcer prevention
- DVT proph.
- IVIG or early plasma exchage beacuse this is autoimmine
- people recover, small chagne of perminence or death
