Neuromuscular Flashcards
Familial ALS gene (FLAS)?
Inheritance?
SOD1 and C9orf72
AD
Spinal Muscular Atrophy (SMA)
1) Gene & Chromosome?
2) What modulated the phenotype?
1) SMN1 Gene on Chromosome 5p (AR dz = 0 fucntioning SMN1 copies)
2) SNM2 copy number modulates phenotype (i.e., more SMN copies correlates with milder symptoms)
Hexosaminidase A deficiency:
1) A/w with accumulation of ________ within _____ ?
2) A/w what disease(s)?
3) T/F - Can be a/w psychiatric features?
Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside.
The prototype hexosaminidase A deficiency is Tay-Sachs disease, also known as the acute infantile variant. Tay-Sachs disease is characterized by progressive weakness, loss of motor skills, decreased attentiveness, and increased startle response beginning between ages three and six months with progressive evidence of neurodegeneration including: seizures, blindness, spasticity, eventual total incapacitation, and death, usually before age four years.
The juvenile (subacute), chronic, and adult-onset variants of hexosaminidase A deficiency have later onsets, slower progression, and more variable neurologic findings, including: progressive dystonia, spinocerebellar degeneration, motor neuron disease, and, in some individuals with adult-onset disease, a bipolar form of psychosis.
Kennedy’s dz:
1) Inheritance?
2) Descriptive name? (sans eponym)
3) Age of onset?
4) Other primary organ system involved?
X-Linked Spinal Bulbar Muscular Atrophy:
Individuals with SBMA have muscle cramps and progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord.
Ages of onset and severity of manifestations in affected males vary from adolescence to old age, but most commonly develop in middle adult life. The syndrome has neuromuscular and endocrine manifestations (e.g., gynecomastia).
Vit B6 (Pyridoxin) TOXICITY:
1) Primarily affects the ____ within the CNS/PNS?
2) Primary exam findings (3)
1) Affects Dorsal root ganglion (Sensory Neuron dz) AKA sensory Neuronopathy:
2) Exam:
- All modality sensory loss
- Ataxia (early Ataxia—–very important finding)
- Areflexia
(normal motor exam/strength)
Vasculitis Neuropathies
Enlarged Hypoechoic nerves on US—-Pathognomonic Usually asymmetric neuropathy (Mononeuritis Multiplex) plus other systemic symptoms eg: Kidney, GI, Skin, fatigue, etc.
Foot INVERSION
- Primary nerve involved?
- Roots?
- Muscle?
Tibial Nerve
(L4-L5)
Tibialis Posterior muscle
Foot Eversion and Dorsiflexion
Primary nerve?
Peroneal Nerve
Myokymic discharges on EMG needle exam
Radiation induced Plexopathy
Patient had lung Cancer, Had XRT, now has plexopathy.
Cancer recurrence or XRT?
If there is Myokymia on EMG it is XRT
Erb’s Palsey (Waiter’s Tip):
1) Two common etiologies?
2) Trunk? Roots?
3) Weakness of ____ ?
4) Sensory loss distribution?
1)
- Most common Plexopathy in newborn
- Common in MVA eg: Motor cycle accident head goes one way and arm the other way.
2) Upper Trunk; C5, C6
3) Weakness: - Shoulder Abd (Deltoid/Axillary N.)
- Elbow flexion(Bicep/Musculocutanous N.)
- Arm Supination
4) Numbness: LATERAL forearm
Klumpke Palsey:
1) Mechanism
2) Trunk involved? Roots?
3) Weakness?
Numbness?
1) Usually occur when arm and shoulder are pulled up
2) Lower Trunk; C8, T1
3) Weakness: Intrinsic hand muscles & wrist flexors –> ‘claw hand’
4) Numbness: MEDIAL forearm (C8, T1 dermatome)
Femoral Nerve (Roots)
Lumbar Plexus; L2, L3, L4
(Same as obturator)
Sciatic Nerve (Roots)
Lumbosacral Plexus; L4, L5, S1
GABA 8 Receptor agonist
Baclofen
Stimulated by GlutamateInhibited by GABA and Glycine
Anterior horn cells
By enzyme:Glutamate Decorboxylase (GAD)GAD65 Ab blocks this enzyme in stiff person syndrome
Glutamate is broken into GABA
Blocks the release of presynaptic GABA and Glycine
Tetanus
Voltage gated K+ channel antibodiesMyokymia is charachteristic(another pathognomonic Myokymia was XRT induced Plexopathy)
NeuroMyotonia
Magnesium/Mg: Blocks Ca++ ChannelsBotulinum: Blocks Ach releaseLathrotoxin (Black Widow): Excessive release of AchTick Paralysis: Blocks Ach realeaseScorpion Venoum: Causes Ach releaseB-Bungarotoxin (Snake Venoum): Inhibits Ach release
Pre-Synaptic Toxins
Curare: Binds nicotinic Ach receptors
Post Synaptic Toxins
Leading cause of death:Bronchospasm and BronchorrheaDUMBELLSS:Diarrhea, Urination, Miosis, Bradycardia, Bronchospasm, Emesis, Lacrimation, Lethargy, Salivation, Seizure
Organophosphatase Poisoning(inhibts acetylchilnestrase so th
Antihistamines, antipsychotics, antidepressants, antiparkinsonian drugs, Atropin, Benztropin, ScopolamineBlurry vision, Hallucination/Delirum, Mydriasis, Ileus, Urinary retention, Flushing, Hyperthermia Blind as a Bat, Mad as a Hatter, Red as a Beet, Hot as a Hade, Dry as a bone
AntiCholinergic symptomsUsually Drug side effect(Reduced Ach
D-PenicillamineCurareBotulinum ToxinInterferon-alphaNeomycine and Quinine are contraindicated.
Meds Absolutely Contraindicated in MG
Steroid MyopathyHyperthyroid MyopathyMitochondrial MyopathyChanelopathies
Myopathies with Normal CK
DystrophionopathiesMyoshi distal myopathyRhabdo, malignant hyperthermia and NMSPolymyositis
Myopathies with Markedly elevated CK
Duchenne’s: Dystrophin is completely absent. Very severe disease. Death by late teens to 20 y.oBecker’s: Dystrophin very reduced. Death by 30-60’sEmery-Dreifuss: Emerin Deficiency. Joint contractures; mostly arms and shoulder. Elbow contracture is pathognomonic for ABPN.
X-Linked MyopathiesMen onlyGowers Maneuver when standing (m
FSHD: face and winged scapula. Popeye appearance (Deltoid and Bicep spared). Big wide eyes, pouting mouth.Oculopharyngeal muscular Dystrophy: French Canadian descent. Ptosis and Dysphagia. No other eye symptoms. If Ptosis and Diplopia think MGLimb Girdle Muscular Dystrophy (LGMD): LGMD type 1 is ADLGMD type 2 is ARMyotonic Dystrophy (DM1) Type 1: CTG repeat. Long face, Temporal wasting, frontal balding, Myotonia (grabs door handles and can’t let go. CARDIAC COMPLCATIONS
Autosomal Dominant Muscular Dystrophies.
LGMD type 2: accounts for 60% of Distal MyopathiesMD2: much less common than MD1. Milder and no cardiac complications
Autosomal Recessive MDs
LGMD type 2Myotonic muscular DystrophyInclusion Body Myositis
Distal Myopathies
Chloride Channel disorder. Get stiff with sitting for a while (Rusted Tin man)Onset age 4-12 yoAD form is milderAR form is more severe
Myotonia congenita
Acid Maltase DeficiencyGlycogen storage diseaseMostly a child disoder but:in Adult: SOB, Proximal Weakness, and Myotonic discharges in Paraspinal muscles (this is the giveaway)It leads to respiratory failure in adults. It’s a Neurologic emergency.TX: IV alpha-Glucosidase
Pompes
Improves with Repetition/exercise
Myotonia
Face muscles; usually eyesMyotonia worsens with repetition.Video of patient closing her eyes and can not open anymore; it’s stuckWorsens with Cold and Hyperkalemia
Para Myotonia Congenita
Familial Hyperkalemic Periodic Paralysis. AD. Na+ ChannelFamilial Hypokalemic Periodic Paralysis. AD. Ca++ ChannelMyophosphorylase Deficiency (McArdle’s dz)Carnitine Palmityl Transferase Deficiency
Imitermittent Myopathies
Children, paralysis minute to hours, Progression variable, Insulin HelpsTreated HIGH Carb dietEMG=Myotonia
HyperK PPADCa++ channel
Adolescent, Paralysis hours to daysProgressive weakness in adulthoodInsuline AggrevatesTreated with LOW Carb dietEMG NO myotonia
HypoK PPADNa+ Channel
Weakness and pain with exercise (hits a wall/Barrier)improve with restGets a second wind
MyoPhosphorylase DeficiencyMcArdles disease
Myoglobulinuria post exercise in fasting stateYoung guy, may be army, forced march without breakfast has severe weakness and very high CKMay be also triggered with Cold and Meds (Advil, Diazepam, general anesthetics)
Carnitine Palmityl Transferase deficiency
Kearns-Sayre Syndrome: MitochondrialOphthalmoplegia; Hearing LossCharacteristic feature: Retinits Pigmentosa and Heart BlocksProgressive External Ophthalmoplegia: MitochondrialOphthalmoplegiaPtosisHearing lossSimilar to MG BUT NO Diplopia
Ophthalmoplegic Myopathies
Painful, Rash, and Muscle weakness (Rash on face, chest, hands, but Elbow knockles, knees are typical because not seen in Lupus)EMG: small motor unitsCan be a/w Breast CaAnti Jo-1 Ab: Indication of Interstitial lung dz
Dermatomyositis
PeriFascicular atrophy/inflammationCD4 predominant
Dermatomyositis Histology
Endomysial inflammationCD8 predominant
Polymyositis Histology
Painless muscle weaknessthe more severe the pain, the less likely it is PolymyositisWoman 40-60may be a/w viral prodrome
Polymyositis
Most common Myopathy in >50 yoDistal muscle weakness and atrophy (Hands/feet)NO FASICULATION, NO HYPERREFLEXIA (DDX with ALS due to the hand atrophy)Rimmed Vacuoles and inclusion bodies on biopsy
Inclusion Body Myositis
