Neuromuscular other Flashcards
from questions and other prep sources
SOD-1 positive ALS rx
Tofersen, an antisense oligonucleotide
ALS non-invasive vent criteria
awake ABG CO2 > 45 mmHG or O2 < 88% for >= 5 min nocturnal recording or PI max >= -60 cmH20, or FVC <50% predicted in upright or supine position
Tibialis anterior innervation
L5 via deep peroneal n.
Tensor Fascia Lata innervation
L4,5 +/- S1 via superior gluteal n.
Abductor Hallucis innervation
S1,2 via tibial n.
Peroneus Longus innervation
L5, S1 via superficial peroneal n.
Medial gastrocnemius innervation
S1,2 via tibial n
Does increased blood pH increase or decrease membrane excitability, and how?
increases excitability
increased pH decreases ionized calcium, making VG sodium channels more easily opened and therefore increases excitability.
Vomiting increases blood pH leading to muscle spasms or tetany
What are three types of incontinence and their characteristics?
stress, urge, and overflow
stress: urethral hyper mobility or sphincter deficiency, leakage with coughing or laughing, pressure injury (obesity or pregnancy)
urge; detrusor hyperactivity, increase urge to urinate, assoc. w Neuro disorders and bladder abnormalities
overflow: impaired depressor contractility, continuous dribbling, associated with Neuro disorders and peripheral neuropathy
Opiod intoxication presentation and rx
depression of MS, RR and tidal volumes, miotic pupils
can have initial euphoria and normal pupils.
Rx Naloxone
Opiod withdrawal: depressed mood, nausea, vomiting, diarrhea, lacrimation, rhinorrhea, dilated pupils. Non-fatal.
Tangier Syndrome
AR, impaired HDL efflux from macrophages, foam cells in macrophages, hepatosplenomegaly and CV disease.
Benzodiazepine withdrawal
life threatening
anxiety, dysphoria, tremors, seizures, psychosis
Fibrillation vs Fasciculation potentials
Fibrillation: regular
Fasciculation: irregular and slow
Fibrillation potentials: loss of normal inhibition such as denervation, inflammation, dystrophy,
or myopathy.
REGULAR repeating pattern and each fibrillation represents the depolarization of a single muscle fiber.
Fasciculation: spontaneous potentials and represent activation of motor unit potentials
at the level of the axon or neuron.
They are slow and IRREGULAR (less than one per
second). End plate spikes are short like fibrillation potentials but repeat IRREGULARLY.
Patella Tendon Reflex physiology
- afferent firing frequency encodes stimulus magnitude
- muscle spindles sense stretch
- Golgi tendon organs sense muscle contraction, type 1b fibers, protects against over-contraction of muscle
- gama motor neurons innervate intrafusal fibers, they prevent intrafusal fibers from becoming slack during contraction to maintain 1a firing during contraction
- alpha motor neurons cause skeletal contraction
Malignant hyperthermia skeletal muscle MOA
excess calcium release from sarcoplasmic reticulum during muscle contraction
Painless myopathies common causes
corticosteroids (MCC), statins, colchicine, chloroquine,
hydroxychloroquine, D-penicillamine, antibiotics, and beta-blockers
Polymyalgia rheumatica key lab finding and rx
elevated ESR, rx low dose prednisone
- almost always seen in patients older than 50 years
- in isolation or in patients with giant cell arteritis.
- CK levels are not increased
with the disease, and while patients may have stiffness and pain, muscle weakness is
not seen and electromyography and muscle biopsy are normal.
Brachial plexus injury prognosis: upper trunk (Erb’s) vs lower trunk (Klumpke)
Upper better prognosis, mostly resolve w/in 1 year
Hereditary sensory and autonomic neuropathy (HSAN) type 2
- AR
- loss of pain, temperature, touch, and pressure sensation in
infancy and early childhood, leads to recurrent infections of the digits,
unintentional self-mutilation, neuropathic joint degeneration, autoamputation, and
fractures. - Deep tendon reflexes are depressed and hypotonia may be present.
- Autonomic involvement is less prominent in HSAN type 2 but may include difficulties with feeding, GERD, apnea, depressed gag reflex, and slowed pupillary response.
- Taste is sometimes
impaired. - HSAN type 2 is genetically heterogeneous.
Muscle biopsy differences denervation vs myopathy
denervation:
* Angulated fibers - due to atrophy.
* Target fibers - created by denervation and reinnervation, with a “bullseye” appearance.
* Small-group atrophy - is another consequence of denervation and reinnervation. Small-group atrophy occurs
when a denervated fiber is reinnervated by a neighboring nerve branch, such that the nerve branch then supplies
at least two contiguous fibers. If that branch then undergoes degeneration, all of the fibers it supplies will
atrophy. This means that a cluster of neighboring fibers will be affected, rather than a single fiber.
* Fiber type grouping - with reinnervation, a nerve branch may supply an increasing number of contiguous fibers.
As a nerve only innervates fibers of the same type, groups of Type 1 or Type 2 fibers will form.
* Clumps of pyknotic nuclei - formed from long-standing fiber atrophy.
A variety of changes may be evident in the setting of myopathy, which may depend upon the specific disorder.
Laminin alpha 2 (merosin) deficiency MD
AR, ch 6
Hypotonia at birth, contractures feet and hips, seizures, WM abnormalities
Laminin is a protein in the basement membrane,
which attaches to dystroglycan. Absence of the protein results in hypotonia at birth,
severe weakness of the trunk and limbs, and contractures of the feet and hips.
Seizures occur in up to 20% of patients.
White matter abnormalities may be evident on imaging.
A partial deficiency causes a milder phenotype.
Brachial Plexus anatomy:
- largest percentage of motor fibers from ?
- largest % motor fibers C5/6
Emery Dreifuss MD (EMD)
deficiency of emerin, a structural
protein of the inner nuclear membrane coded by the STA gene.
X-linked inheritance.
Slowly progressive weakness affects the anterior legs, upper arms, and shoulders.
Early contractures - elbows, neck, ankles.
The disorder is associated with cardiomyopathies.
Ulrich’s Congenital Muscular Dystrophy (UCMD)
Hypermobility and protrusion of calcanei
presents with neonatal weakness and multiple
contractures
AR or AD or sporadic
collagen type VI mutations (i.e. Ulrich’s congenital muscular dystrophy).
Limb Girdle Muscular Dystrophy LGMD
Dysferlin deficiency (limb girdle muscular dystrophy type 2B) is caused by a mutation
on chromosome 2, of autosomal recessive inheritance. Onset is typically in the
teenage or early adult years.
Sarcoglycan deficiency causes limb girdle muscular dystrophies of types 2C, 2D, 2E,
and 2F. The disorders are of autosomal recessive inheritance, and lead to trunk and limb
weakness with calf hypertrophy.
CMV Neuropathy
CMV directly infects peripheral nerves, causing
inflammation and necrosis.
advanced AIDS
Mononeuropathy multiplex
classic manifestation of CMV neuropathy is a mononeuropathy multiplex,
characterized by painful, stepwise, multifocal sensorimotor deficits.
It may be rapidly progressive, with nerve injury due primarily to axonal degeneration, although
segmental demyelination may also be present.
CMV may also result in a cauda equina
syndrome, with lower extremity weakness and numbness, and sphincter dysfunction,
due to axonal injury.
Miyoshi Myopathy
AR, ch 2
present 19-20 yo
distal weaness/atrophy - medial Posterior cal gastrocnemius, and adductor Magnus
dysferlin on Ch 2p
CK 20-150 x f normal
Bethlem Myopathy
AD
progressive, VI collagen, proximal weakness and flexion contractures
Bethlem myopathy is a rare congenital muscular dystrophy with an autosomal dominant (AD) inheritance pattern. It is caused by mutations in one of the genes encoding collagen VI: COL6A1, COL6A2, or COL6A3. These mutations lead to defects in collagen VI, a crucial extracellular matrix protein involved in maintaining muscle integrity and stability.
Key Features of the Inheritance Pattern
1. Autosomal Dominant (Most Common):
• One copy of the mutated gene (from one parent) is sufficient to cause the disorder.
• Affected individuals typically have an affected parent.
• A 50% chance of passing the mutation to offspring with each pregnancy.
2. Rare Autosomal Recessive Cases:
• In rare cases, autosomal recessive inheritance can occur due to biallelic mutations in one of the collagen VI genes.
• Requires both parents to be carriers, with a 25% chance of an affected child.
Clinical Correlation
• Bethlem myopathy often presents with:
• Proximal muscle weakness (e.g., shoulders and hips).
• Joint contractures, particularly in the elbows, ankles, and fingers.
• Gradual progression, typically milder than other muscular dystrophies.
• Onset can vary from early childhood to adulthood.
Diagnostic Approach
1. Genetic Testing:
• Identifies mutations in COL6A1, COL6A2, or COL6A3.
• Can confirm autosomal dominant or recessive inheritance patterns.
2. Muscle Biopsy:
• May show reduced or abnormal collagen VI staining in the extracellular matrix.
3. Family History:
• Helps identify the dominant inheritance pattern if multiple family members are affected.
Understanding the inheritance pattern is critical for genetic counseling, especially in families planning for children.
H reflex
The H reflex is a reflex with an afferent and efferent arc, mediated by large la fibers
and alpha motor fibers
Need submaximal stimulation and is
most consistently seen when evaluating S1 by stimulating the tibial nerve at the
popliteal fosse and recording from the soleus or plantar muscles of the foot.
F wave
supramaximal nerve stimulation motor nerve resulting from electrical activity that propagates antidromically after the M wave, which represents the direct
motor response to electrical stimulation.
Calpain-3 deficiency
- onset of symptoms in childhood or early adulthood.
AR, Ch 15
Scapular winging, weakness of the muscles of the posterior thigh, and rectus abdominus weakness are typically seen early in the course of the disease.
Loss of ambulation occurs in adulthood. No treatment is available.
Myotilin deficiency
C. Myotilin deficiency (limb girdle muscular dystrophy type 1A) presents with weakness
in the second or third decade. The proximal arms are typically more severely affected
than the legs.
AD, Ch 5
Facioscapulohumeral (FSH) Muscular Dystrophy
AD, Ch 4
asymmetric weakness face and shoulder girdle and scapular winging, weak abdomen (Beevor Sign) LE weakness too
16 yo males and 20 yo females
Diabetic Amyotrophy
pain, weakness, and wasting of the pelvifemoral muscles
asymmetric but may affect the contralateral side
Sensory impairment is usually minimal or absent.
DTRs are reduced or absent in the patella in the affected extremity or in both extremities, but the ankle jerk reflex may be normal or only
slightly diminished.
onset is in middle age or later, and men are affected more often than women.
DM2>1
Electrodiagnostic studies show denervation in the involved muscle groups.
onset rapid and may occur shortly after diagnosis of DM
RX: aggressive glycemic control and physical therapy. Patients may gradually recover strength over a period of months and
sometimes years.
Erythromelalgia Syndrome
Inherited or acquired.
Inherited is AD, SCN9A gene, which encodes a voltage-gated sodium channel (
hyperexcitability to peripheral sensory and sympathetic neurons)
episodes precipitated by exposure to increased temperature during which the affected area becomes hot, red, and painful.
Over months to years, symptoms progress, and
patients experience more frequent episodes lasting for longer periods of time.
- relieved by cooling the area, patients’ immerse the affected area in cold water to relieve symptoms.
Between episodes, the affected area is
acrocyanotic and cool in up to 66% of patients. Feet are affected in most patients, although hand involvement occurs in 25%. The head and neck and extremities may also be involved. Symptoms are usually symmetric.
The mechanism may be a microvascular AV shunt. The disorder is also associated with small- and large-fiber
neuropathy, with abnormal thermoregulatory sweat testing and abnormal quantitative sudomotor axon reflex testing in 90% and 80% of
patients, respectively.
A 16-year-old female is evaluated for chronic recurrent episodes of burning pain and redness in her feet that are exacerbated by warm weather and exercise.
She cools her feet in ice cold water several times a day to relieve her symptoms. The episodes usually last an hour or more before resolution and seem to be
worse at night. She reports that she has experienced similar discomfort and redness in her feet since she was 13 years old, but her symptoms have
progressively worsened. Her mother has similar symptoms that are present most of the day despite using opioid analgesics and spending hours daily cooling
her feet. Her medical history is otherwise unremarkable. She is currently asymptomatic.
S1 Radiculopathy
plantar flexion
eversion of foot
ankle jerk
L 5 Radiculopathy
extension of big toe (extensor hallucis longus)
tibialis anterior - dorsiflexion and inversion
tensor fascia latae
Tangier Syndrome
AR
impaired HDL mediated cholesterol efflux from macrophages
ATP binding cassette transporter A1 genes on Ch 9
foam cells
cholesterol deposition in tonsils - orange tonsils, liver, spleen GI tract, lymph nodes, bone marrow, and Schwann cells
hepatosplenomegaly and CV disease
There are 2 primary types of Tangier syndrome: a peripheral neuropathy characterized by distal sensory loss, fluctuating numbness, tingling,
and distal weakness with muscle atrophy; and a syndrome characterized by progressive loss of sensorimotor function that begins in the
upper extremities, similar to syringomyelia.
Muscle biopsy denervation findings
target fibers created by denervation and re-innervation w bullseye appearance
angulated fibers due to atrophy
small group atrophy
fiber type grouping
clumps of pyknotic nuclei formed from long standing fiber atrophy
Muscle biopsy myopathy findings
- Central nuclei - which are particularly common in muscle dystrophies.
- Necrosis of muscle.
- Fiber size variation.
- Fiber splitting - by a thin fibrous septum.
- Basophilic appearance of regenerating fibers. * Inflammatory reactions.
- Muscle fibrosis - thickening of the connective tissue surrounding individual fibers.
- A moth-eaten, whorled appearance of fibers.
Multifocal Motor Neuropathy w conduction block
anti-GM1 abs (may be present in ALS in low titers)
normal CSF
CMAP w demyelinating features
RX: IVIG effective for most patients, if fails try cyclophosphamide
UE>LE, distal > proximal
NO UMN findings, similar to PMA
Mixed Cryoglobulinemia Type 2
Clinically, cryoglobulinemia is characterized by nonspecific constitutional symptoms, arthralgias, lymphadenopathy, peripheral neuropathy,
and cutaneous findings that include palpable purpura and erythematous macules, usually found on the lower extremities.
Melzer’s triad is the classic presentation of arthralgia, weakness, and purpura associated with type 2 cryoglobulinemia.
Peripheral nerve involvement has been reported by 30-45% of patients, but severe peripheral neuropathy, including mononeuritis multiplex
or combined sensorimotor neuropathy, is rare.
Mixed cryoglobulinemia is commonly associated with viral infections, particularly chronic
HCV infection. Other cases primarily occur in patients with connective tissue disease or lymphoproliferative disorders. Treatment includes
immunosuppressants (rituximab) and treatment of the underlying disease.
What are dematosomal somatosensory evoked potentials used for?
document multiple or single root involvement in spinal stenosis
Lumbosacral plexus derived from which rami of which nerve roots?
anterior rami T12-S3
What are the major nerves of the lumbar plexus and their nerve roots?
Lateral femoral cutaneous nerve: L2,3
Femoral nerve: posterior divisons L2,3,4
Obturator nerve: anterior divisions L2,3,4
Sciatic nerve composed of
lumbosacral trunk (L4,5) which joins Sacral plexus to form sciatic nerve.
Tibial division from anterior primary rami L5-S2
Common Peroneal division from posterior divisions of anterior rami L4-S2
Sacral Plexus derived from:
L4-S4 (with L4,5 from lumbosacral trunk)
Fukuyama congenital MD (FCMD)
AR
Fukuyama type congenital muscular dystrophy (FCMD) is characterized by diffuse weakness, early contractures of the hip, knee, and ankle,
intellectual disability, seizures, skull asymmetry, and cerebral malformations. The structural malformations may include cobblestone cortex
(a nodular appearance of the gray matter), loss of gray matter lamination, and frontal white matter changes. Infants typically have normal
strength, with progression of the disease and death in early childhood. The disorder is of autosomal recessive inheritance, due to
chromosome 9 mutations affecting the gene for fukutin. The enzyme is associated with the Golgi complex and glycosylates other proteins. As
a-dystroglycan is glycosylated, its function may be affected by FCMD.
Congenital Myotonic Dystrophy
Congenital myotonic dystrophy occurs in newborns of mothers with myotonic dystrophy, and is due to large CTG repeats in the myotonic
dystrophy protein kinase (MDPK) gene on chromosome 19. It is manifested by hypotonia and facial paralysis, resulting in respiratory
insufficiency and failure to thrive. The mouth has a characteristic inverted “V” shape, due to the facial weakness. The disorder is associated
with club feet and intellectual disability.
Brachioradialis muscle aka supinator longus
radial nerve (C5,6 (7))
supinator
Treatment related neuropathy vs diabetic neuropathic cachexia
Treatment-related neuropathy in patients with diabetes is a painful sensory neuropathy
that develops acutely after initiation of strict blood glucose control. Diabetic
neuropathic cachexia is similar in symptomatology, with the additional feature of severe
weight loss.
Nonaka Myopathy
AR
Ch 9 (same locus at IBM w sparring of quads)
anterior tib.
early adulthood
progressive to forearm and hand
wheelchair if distal myopathy
Spasticity results from:
Spasticity results from overactivity of the a-motoneurons innervating the skeletal
musculature.
Under normal circumstances, these a-motoneurons are tonically
stimulated by reticulospinal and vestibulospinal fibers originating in the brain stem.
These brain stem fibers are normally inhibited by fibers originating in the cortex. Cutting
the corticoreticular fibers releases the brain stem fibers from inhibition and results in
spasticity.
Hereditary Sensory and Autonomic Neuropathy (HSAN) type 1
progressive loss of small and large nerve fibers. These disorders are
classified by inheritance pattern, age of onset, and clinical manifestations.
HSAN type 1,
the most common classification, includes variants with primarily autosomal-dominant
inheritance and an onset usually in the second or third decade of life. Clinical
characteristics include initial symptoms of pain and sensory loss in the lower
extremities, followed by motor weakness. Distal sensory loss is followed by
neurotrophic foot ulcers. Patients may develop osteomyelitis, neuropathic arthropathy,
spontaneous fractures, and bone necrosis as a result. Complete loss of sensation occurs
over time, except for preservation of facial sensation. Distal muscle weakness and
atrophy are variable. Autonomic involvement typically results in changes in sweating.
HSAN type 1 may be associated with deafness, hypacusis, coughing, and GERD.
disorder is disabling, and treatment commendations include foot care as in diabetic
peripheral neuropathy.
Syringomyelia
very slow progression
Atrophy starts in the hands, along with weakness and dissociated sensory loss (the syrinx disrupts the decussating
spinothalamic fibers mediating pain/temp, but light touch/vibration/position are
preserved).
Pain and temperature sensation may also be impaired in a “shawl-like”
distribution across the shoulders, and symptoms can also include dysesthesia in the
neck/shoulders or radicular pattern and ulcers, edema, or hyperhidrosis in the hands.
Patients may also present with diminished arm reflexes and claw hands. Treatment is
surgical.
Wartenberg Syndrome
Superficial Sensory Radial neuropathy
tennis and other sports requiring lots of pronation/supination
pain and pareasthesias over dorsolateral hand and dorsal thumb
pure sensory nerve
Carpal Tunnel Syndrome
pregnancy, hypothyroidism, RA, diabetes, amyloidosis
unilateral or bilateral (most common)
median nerve and 9 flexor tendons including flexor polllicis Longus
Pseudobulbar Palsy
increased jaw jerk and gag reflex
aka involuntary emotional expression disorder
Pseudobulbar palsy, also known as involuntary emotional expression disorder, is a
condition that affects ability to control of the facial muscles (including the jaw). The
muscles in the mouth (i.e. your tongue) and throat can also be affected. It is
characterized by progressive loss of the ability to speak, chew, and swallow. Progressive
weakness in facial muscles leads to an expressionless face. Individuals may develop
dysarthria and an increased gag reflex, in addition to increased jaw jerk.
In addition to these symptoms, one may experience uncontrollable crying or laughing at
inappropriate times. This is known as pseudobulbar affect or “emotional incontinence.”
Pseudobulbar palsy is common in stroke patients and those with neurological disorders
such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
Median Nerve anatomy
The median nerve is composed of fibers from the nerve roots of C5 (variable), C6, C7, C8,
and T1, originating in the axilla from branches of the medial and lateral cords of the
brachial plexus just anterior to the axillary artery. It supplies motor innervation to the
anterior forearm muscles with the exception of flexor carpi ulnaris and the lateral half of
flexor digitorum profundus. It also supplies motor fibers to the thenar muscles and
provides sensory innervation to the lateral two-thirds of the palm and the dorsal
fingertips of the first through third digits.
In the arm, the median nerve is closely related to the brachial artery before it enters the
cubital fossa medial to the brachialis tendon and passes between both heads of the
pronator teres. The anterior interosseous nerve branches from the median nerve in the
pronator teres. Traveling down the forearm between the flexor digitorum profundus and
the flexor digitorum superficialis, the median nerve then follows its course between the
flexor digitorum superficialis and the flexor carpi ulnaris muscles, proximal to the wrist.
The palmar cutaneous branch of the median nerve originates proximal to the wrist and
supplies the skin of the central portion of the palmar surface of the hand. The median
nerve travels through the carpal tunnel, anterior and lateral to the tendons of the flexor
digitorum superficialis, to enter the hand, where it splits into a muscular branch and
palmar digital branches. The muscular branch supplies the thenar eminence, while the
palmar digital branch supplies sensation to the lateral two-thirds of the palmar surface
of the digits and first through third dorsal fingertips.
Pure Autonomic Failure aka idiopathic orthostatic hypotension
mid to late adulthood
Orthostatic hypotension is a predominant symptom, although men may initially present with
impotence.
Other sis: hypohidrosis; urinary symptoms that may include nocturia,
frequency, urgency, hesitation, and episodic incontinence; and early satiety and nausea
resulting from hypomotility of the gastrointestinal (GI) tract.
pain in the neck and shoulders exacerbated by standing and relieved by lying down.
Symptoms are exacerbated after meals, with exertion, or with exposure to a warm
environmental temperature.
Often worse in the morning.
May be 2/2 deposition of A-synuclein in the autonomic
nervous system, resulting in the loss of intermediolateral cell column neurons in the
spinal cord.
Autonomic Autoimmune Ganglionopathy
Subacute onset of autonomic dysfunction
Antibodies against ganglionic nicotinic acetylcholine receptors (g-AChR antibodies) are
present in about 50% of patients. Other autoantibodies may be responsible in
seronegative individuals. Sixty percent of patients have a history of antecedent
infection.
Sxs; cholinergic deficit, including orthostatic hypotension, neurogenic bladder, and gastroparesis, as
well as anhidrosis, dry eyes, and dry mouth. Pupils react slowly to light and
accommodation.
No sensory or motor impairment, DTR normal
Women are twice as likely as men, middle age usually
Patients may have another autoimmune disorder.
Paraneoplastic autonomic dysfunction should be excluded. Patients typically experience monophasic
onset of symptoms, and recovery is usually incomplete.
Treatments include immunosuppressants, IVIG, and plasmapheresis.
What condition is associated with atlantoaxial dislocation?
Down syndrome
Myokymia associated with:
GBS
Intramedullary pontine tumor
Radiation therapy
Inflammatory demyelinating disease
Myokymia is an involuntary spontaneous quivering of a few muscle fibers or bundles within a muscle insufficient
to move a joint. Movements are described as coarse, and more sustained as compared to fasciculations, which
can have a rippling quality. Myokymia is often associated pathologies that involve denervation. Stroke is not one
of the commonly associated disorders causing myokymia. Radiation therapy is an important one to remember. A
majority of patients have myokymic discharges detected within the field of prior radiation therapy. Myokymia has
reported even with low radiation doses.
Walker-Warburg Syndrome
AR, Ch 9
muscular dystrophy, cerebral and eye malformations
death w in 2 yrs
Thoracoabdominal Polyradiculopathy
non-radicular truncal pain and abdominal bulging/swelling
thought to be an ischemic polyneuropathy and is usually unilateral but may be bilateral. Electrodiagnostic studies show fibrillations and sharp waves of affected muscles in the abdominal wall and paraspinal muscles in the involved dermatomes, with an increased proportion of polyphasic motor unit potentials and decreased interference
patterns.
frequently mistaken for other gastrointestinal or intraabdominal processes, and patients may undergo extensive Gl evaluation prior to diagnosis.
Recovery may occur spontaneously or with the treatment of diabetes, although the length of recovery may be several months.
Pain may respond to anti-inflammatory agents in addition to carbamazepine, phenytoin, or amitriptyline.
