PMR 5 - neuromuscular disorders Flashcards
Which of the following motor neuron diseases typically causes both upper and lower motor neuron signs?
a. Spinal muscle atrophy lI
b. Primary lateral sclerosis (PLS)
c. Amyotrophic lateral sclerosis (ALS)
d. Poliomyelitis
C) Weakness may be due to upper or lower motor neuron loss. Upper motor neuron (UMN) signs include weakness, spasticity, hyperreflexia, and upgoing plantar response.
Lower motor neuron (LMN) signs include weakness, atrophy, flaccidity, hyporeflexia, and fasciculations. ALS patients with UMN pathology will often have a loss of dexterity or feeling of stiffness in their limbs. Spasticity may further exacerbate weakness and loss of function. This is due to the involvement of the vestibulospinal and reticulospinal tracts. LMN symptoms in the ALS population include ( muscle weakness, with some muscle fasciculations, atrophy, and muscle cramping.
Cramping of abdominal or other trunk muscles should prompt a clinician to strongly consider ALS as a possible diagnosis.
Primary lateral sclerosis (PLS is classified as an UMN lesion. Spinal muscle atrophy II (SMA II) and poliomyelitis are classified as LMN lesions.
A 60-year-old man without any significant past medical history presents to vour outpatient office with asymmetric atrophy, weakness, and fasciculations.
He also complains of some difficulty swallowing his meals and complains of a strained and strangled quality in his speech. He describes normal bowel and bladder function. Which of the following is most likely his diagnosis?
a. Amyotrophic lateral sclerosis (ALS)
b. Spinal muscle atrophy III
c. Primary lateral sclerosis (PLS)
d. Poliomvelitis
A) ALS most commonly affects people in the age group of 40 to 60 years, and the mean age of onset is around 60 years. Onset is > usually insidious and painless. Asymmetric weakness is the most common presentation.
Dysphagia (oral, pharyngeal), dysarthria, drooling, and aspiration can occur and are signs and symptoms representing bulbar muscular weakness. Also, strained, strangled quality of speech, reduced rate, and low pitch indicate a spastic dysarthria. Bowel and bladder function is typically spared in ALS.
Which of the following is considered a poor prognostic factor in patients with amyotrophic lateral sclerosis (ALS)?
a. Predominance of upper motor neuron (UMN) findings at diagnosis
b. Long period from symptom onset to diagnosis
c. Younger age of onset
d. Pulmonary dysfunction early in the clinical course
D) Poor prognostic factors include predominance of lower motor neuron (LMN)
findings at diagnosis, short period from symptom onset to diagnosis, and older age at time of onset. Bulbar and pulmonary dysfunction early in the disease course is also a poor prognostic factor. Women typically present with bulbar symptoms, as compared with men. It is important to note that electrodiagnostic indicators of poor prognostic indicators include profuse spontaneous fibrillations, positive sharp waves, and low-amplitude compound muscle action potential.
What is the prognosis for patients with amyotrophic lateral sclerosis?
a. 50% die within 3 years
b. 100% die within 3 years
c. 50% live up to 7 years
d. 50% live up to 10 vears
A) The overall median 50% survival rate is
2.5 years after diagnosis. Survival rate is largely dependent on a patient’s decision to use mechanical ventilation and/or a feeding tube, but the 5-year survival rate is between 4% and 30%. Around 10% will live for 10 years.
Which of the following pharmacologic agents has been approved for patients with amyotrophic lateral sclerosis (ALS)
to slow the progression and improve survival?
a. Levodopa
b. Riluzole
c. Baclofen
d. Rebif
B) This is an antiglutamate agent that may be effective in slowing the disease, prolonging ventilator time, and may improve survival in patients with bulbar onset disease.
However, side effects can include asthenia, and the medication is expensive.
Nonpharmacological management of ALS includes rehabilitation, preventing contractures, submaximal exercise, tracheostomy, and respiratory therapy. Rebif is a beta interferon that is used to modify the course in multiple sclerosis patients. Baclofen is a derivative of gamma-aminobutyric acid (GABA) and is primarily used to treat spasticity. Levodopa is a medicine used to control symptoms of Parkinson’s disease.
Levodopa does not slow the disease process, but it improves muscle movement and delays severe disability.
Which of the following motor neuron diseases typically causes lower motor neuron signs and has the earliest disease onset?
a. Kugelberg-Welander disease
b. Primary lateral sclerosis (PLS)
c. Amyotrophic lateral sclerosis (ALS)
d. Werdnig-Hoffmann disease
D) Upper motor neuron signs include weakness, spasticity, hyperreflexia, and upgoing plantar response. Lower motor neuron signs include atrophy, flaccidity, hyporeflexia, and fasciculations. Werdnig-Hoffmann disease is also known as spinal muscular atrophy type I, or acute infantile-onset SMA. This severe disorder often results in death by the age of 2, and disease onset is 3 to 6 months. Recent studies have shown that there is a reported increase in longevity, most likely a result of better overall medical management. However, SMA type I carries the worst prognosis of all the forms of SMA, as patients may never be able to reach the childhood milestone of sitting independently.
The disease course is rapid and fatal secondary to respiratory failure. SMAll and III have later onset, and progression is generally slower. Kugelberg-Welander disease is also called SMA type III. All forms of spinal muscle atrophy are classified as lower motor diseases. PLS is an upper motor neuron disease, and ALS is classified as both upper and lower lesion motor disease.
A 16-year-old male presents to your office with concerns that recently he uses his hands and arms to “walk” up his own body from a squatting position.
He states that he was otherwise independent with standing and walking and has been doing well as a student and plans on attending college. Which lower motor neuron disease does he most likely have?
a. Spinal muscular atrophy (SMA) type I
b. SMA type lI
c. SMA type III
3d. Amyotrophic lateral sclerosis (ALS)
C) SMA type III (spinal muscular atrophy) is also known as Kugelberg-Welander disease.
The disease onset is later than that of type I and II, occurring between 2 and 15 years of age. Patients typically live a normal life expectancy. The progression is slower than the other two variants. Patients usually achieve independent standing/walking. This patient presents with Gower’s sign, which can be seen in SMA type III patients because proximal weakness is greater than distal weakness. These patients typically have normal intelligence. Complications in SMA III are less frequent, but may include hand tremor, tongue fasciculations (late onset), and areflexia. All forms of spinal muscle atrophy are classified as lower motor diseases, and ALS is classified as both upper and lower lesion motor disease.
A patient with spinal muscular atrophy
(SMA) type iI (chronic Werdnig-Hoffmann) can usually achieve which of the childhood milestone below?
a. Assisted sitting
b. Independent sitting
c. Independent standing
d. Independent ambulation
B) SMA type Il is also known as chronic Werdnig-Hoffmann. The disease onset is between 2 and 12 months, and death (often by respiratory failure) occurs by 10 years of age.
These patients can usually achieve.
milestones including independent sitting.
They may be able to stand or walk with an assistive device. Answer choice D is therefore incorrect and refers to someone with SMA type III. SMA type I patients never attain the ability to sit independently, and this severe disorder usually results in death by the age of 2.
Which of the following motor neuron diseases has the best prognosis?
a. Kugelberg-Welander disease
b. Chronic Werdnig-Hoffmann
c. Werdnig-Hoffmann disease
d. Both B and C, as their clinical course is similar
A) Spinal muscular atrophy (SMA) type lis also known as Werdnig-Hoffmann disease.
Death usually occurs by 2 to 3 years of age.
The progression is rapid and fatal. Patients with SMA type II, known as chronic Werdnig-Hoffmann, usually die by about 10 years of age. Again, the progression is fatal. Patients with SMA type IlI, known as Kugelberg-Welander disease, have a normal life expectancy with a slow progression.
Which of the following pharmacologic agents is a first-line treatment for spasticity in patients with amyotrophic lateral sclerosis (ALS)?
a. Tizanidine
b. Dantrolene
c. Benzodiazepine
d. Baclofen
D) Baclofen is a GABA analogue used to facilitate motor neuron inhibition at spinal levels and is the first-line treatment. Dosing can be started at 5 to 10 mg two to three times per day. It can be titrated up to 20 mg four times per day. Potential side effects include weakness, fatigue, and sedation. Patients must be informed that abrupt discontinuation of baclofen may cause withdrawal seizures. Tizanidine is an alpha-2 agonist.
Benzodiazepine can be helpful, but can cause respiratory depression and somnolence.
Dantrolene blocks calcium release in the sarcoplasmic reticulum and is ineffective at reducing muscle tone, but can cause generalized muscle weakness.
Which of the following is the most common presenting form of motor neuron disease in adults?
a. Amyotrophic lateral sclerosis (ALS)
b. Poliomyelitis
c. Spinal muscular atrophy (SMA)
d. Primary lateral sclerosis (PLS)
A) ALS is also called Lou Gehrig’s disease, as it was named after the New York Yankees’ first baseman who passed away from this disorder. This is unfortunately still the most widely known motor neuron disease and is the most common presenting form. The incidence of ALS is approximately 1.6 to 2.4 cases per 100,000 population.
Which of the following is not included in the Halstead and Rossi (1987) criteria in defining postpolio syndrome?
a. History of previous diagnosis of polio
b. Stability for approximately 5 years
c. Recovery of function
d. No other medical problem to explain new symptoms of weakness/atrophy
B) The answer choice would be correct if it was stability for approximately 15 years.
Postpolio syndrome is a diagnosis based on exclusion. It has been well defined by the Halstead and Rossi criteria (1987): 1.
Confirmed history of poliomyelitis 2. Partial to fairly complete neurologic and functional recovery 3. A period of neurologic and functional stability of at least 15 years in duration 4. Onset of two or more of the following health problems since achieving a period of stability: unaccustomed fatigue, muscle and/or joint pain, new weakness in muscles previously affected and/or unaffected, functional loss, cold intolerance, new atrophy 5. No other medical diagnosis to explain these health issues.
Which virus has been implicated in the development of poliomyelitis?
a. Herpes virus
b. Papillovirus
c. Picornavirus
d. Poxvirus
C) Acute poliomyelitis is a disease that causes degeneration of the anterior horn cell, and is caused by the polio virus. The polio virus is a small RNA virus belonging to the enterovirus group of the picornavirus family.
Picornavirus orally enters the body and spreads via lymphoid system leading to orphaned muscle fibers and potential central nervous system involvement. All other answer choices are DNA viruses.
Of the following, which is a disorder of neuromuscular transmission due to an autoimmune response against acetylcholine receptors on the postsynaptic membrane?
a. Myasthenia gravis.
b. Lambert-Eaton myasthenic syndrome (LEMS)
c. Botulism
d. Amvotrophic lateral sclerosis (ALS)
A) Neuromuscular junction disorders can be classified into two categories: presynaptic or postsynaptic. LEMS and botulism are presynaptic disorders, and myasthenia gravis is a postsynaptic disorder. Myasthenia gravis is a disorder resulting in a decreased quantal response because of an autoimmune response against acetylcholine receptors on the postsynaptic membrane. LEMS is a disorder of neuromuscular transmission due to an autoimmune response against the active sites on the presynaptic membrane. Botulism is a disorder of neuromuscular transmission caused by Clostridium botulinum toxins blocking exocytosis of acetylcholine from the nerve terminal. ALS is a motor neuron disease that presents with both upper and lower motor neuron lesions that is caused by degeneration of the anterior horn cell
What is the etiology of Lambert-Eaton myasthenic syndrome (LEMS)?
a. Disorder of neuromuscular transmission caused by
Clostridium botulinum toxins blocking exocytosis of acetvicholine from the nerve terminal
b.Disorder of neuromuscular transmission caused by C. botulinum toxins blocking endocytosis of acetylcholine from the nerve terminal
c. Disorder resulting in a decreased quantal response because of an autoimmune response against acetylcholine receptors on the postsynaptic membrane
d. Disorder of neuromuscular transmission due to an autoimmune response against the active sites on the presynaptic membrane
D) This decreases calcium entry into the cell, causing a decreased release of acetylcholine into the synaptic cleft. There is a strong association with malignancy, such as small cell (oat cell) carcinoma of the lung.
Answer choice A describes botulism, and answer choice C describes myasthenia gravis.
A 45-year-old man presents to your office with complaints of fatigue and weakness that are exacerbated with rest and often improved with exercise. He denies vision disturbances bilaterally.
On physical exam, there is notable weakness in bilateral quadriceps. Which neuromuscular junction disorder may he have, and which location is affected?
a. Myasthenia gravis (MG);
postsynaptic
b. Lambert-Eaton myasthenic syndrome (LEMS); presynaptic 3 c. Myasthenia gravis; presynaptic
d. LEMS; postsynaptic
B) LEMS is a disorder of neuromuscular transmission due to an autoimmune response against the active sites on the presynaptic membrane. Patients complain of proximal fatigue and weakness that affects mainly the lower limbs, such as the quadriceps.
Symptoms are exacerbated with rest and improved with exercise. Rarely are there neck, facial, or bulbar muscle involvements. It is important to note that there is sparing of ocular muscles. There is also often an association with malignancy, most commonly oat cell carcinoma of the lung. Onset occurs more in males than in females (2:1) and in those older than 40 years. Unlike MG, LEMS patients may experience an increase in strength after a series of muscle contractions.
A 49-year-old woman presents to your clinic with complaints of fluctuating double vision and droopy eyelids. The patient is sent for a test where edrophonium chloride is injected, and there is brief improvement in her symptoms. Which of the following does she most likely have?
a. Myasthenia gravis (MG)
b. Lambert-Eaton myasthenic syndrome (LEMS)
c. Botulism
d. Amyotrophic lateral sclerosis (ALS)
A) Myasthenia gravis patients may complain of proximal muscle fatigue and weakness exacerbated with exercise, heat, or time of day (evening). It is important to note that there can be facial or bulbar symptoms, including ptosis, diplopia, dysphagia, or dysarthria. This patient presents with ocular myasthenia gravis. Ocular involvement is an extremely common initial presentation in MG patients. Drooping of eyelids and intermittent diplopia result from levator palpebrae (extraocular muscles) involvement, which is seen in 90% of MG cases. The test here describes the edrophonium (Tensilon) test.
An intravenous solution of edrophonium chloride is injected into a patient. A total of 10 mg of the cholinergic drug is prepared, and a
2-mg dose is injected. If there is no reaction in
30 seconds, the remaining 8 mg is administered. A brief improvement in muscle activity is regarded as a positive result.
Edrophonium chloride is also used to distinguish between myasthenia gravis and a cholinergic crisis. Because edrophonium chloride can precipitate respiratory depression, the test should not be performed unless an anticholinergic antidote, such as atropine, and respiratory resuscitation equipment are available.
A 49-year-old female presents to your clinic with complaints of fluctuating double vision 18. and droopy eyelids.
The patient is sent for a test where edrophonium chloride is injected, and there is brief improvement in her symptoms. Which of the following treatments is most appropriate?
a. Trivalent ABE antitoxin
b. Guanidine
c. Treat the malignancy
d. Mestinon
D) Mestinon (pyridostigmine) reversibly binds to and inactivates acetylcholinesterase, which is a cholinesterase inhibitor. This patient has myasthenia gravis (MG). Mestinon 60 to 120 mg orally every 3 to 8 hours can be used to treat MG. Other treatment options for MG include thymectomy, corticosteroids, immunosuppressive agents, and plasmapheresis. Answer choice C is correct in Lambert-Eaton myasthenic syndrome (LEMS) patients with malignancy. Initial treatment should be aimed at the neoplasm because weakness frequentlv improves with effective cancer therapy. No further LEMS treatment may be necessary in some patients.
Answer choice A is used for patients with botulism.
Symptoms of botulism present how soon after spore ingestion?
a. 1 hour
b. 2 to 4 hours
c. 1 day
d. 1 month
C) Symptoms such as blurred vision and diplopia can occur, along with nausea and vomiting, between 12 and 36 hours after consuming raw meat, fish, canned vegetables, or honey, making answer choice C the best answer. Bulbar symptoms are noted first and include ptosis, dysphagia, or dysarthria.
Gastrointestinal symptoms include nausea and vomiting, and then there may be widespread paralysis or flaccidity. If severe, there may be respiratory dysfunction. Lab work may reveal botulinum toxin in the stool or blood serum. Recovery occurs from collateral sprouting of nerves.
A 4-year-old boy is brought into your office because his mother has noticed that he has difficulty getting up from a seated position on the floor while playing with his toys. On physical exam, there is increased gastrocnemius calf circumference bilaterally. You think the child may have dystrophic myopathy.
The maneuver the child performs to assist him in standing is caused by:
a. Proximal leg weakness
b. Distal leg weakness
c. Proximal arm weakness
d. Distal arm weakness
A) The maneuver noted here is Gower’s sign, which is the inability to rise from a seated position on the floor. The patient has to use his hands and knees for assistance in a fourpoint stance. He will bridge the knees into extension and leans the upper extremity forward. This will substitute hip extension weakness (proximal leg weakness) and lean the upper extremities forward. The patient then moves the upper extremities up the thigh, and a full hip extension is achieved in an upright stance. The Gower’s sign indicates proximal muscle weakness. Also, this patient has pseudohypertrophy, which is seen in patients with either Duchenne or Becker’s muscular dystrophy. The enlargement in the calf is not due to increased muscle. It is a result of increased fat and connective tissue.
Which myopathy is characterized by a steadily progressive, X-linked muscular dystrophy that is characterized by absent dystrophin or less than 3% that is normal?
a. Becker’s muscular dystrophy (BMD)
b. Duchenne muscular dystrophy (DMD)
c. Limb-girdle muscular dystrophy (LGMD)
d. Facioscapulohumeral dystrophy (FSHD)
B) DMD is an X-linked disorder with an abnormality in the Xp21 gene locus. There is dystrophin deficiency that disrupts the membrane cytoskeleton and leads to membrane instability. Chronically, this will lead to fibrotic replacement of muscle and failure of regeneration, with muscle fiber death. Absent dystrophin or less than 3% of normal is diagnostic of DMD. Becker’s is also an X-linked disorder, but quantitative dystrophin analysis shows either 20% to 80% dystrophin levels. Answer choice C and D are not X-linked disorders.
Becker’s muscular dystrophy is characterized by:
a. Autosomal dominant condition
b. Autosomal recessive condition
c. X-linked, absent dystrophin
d. X-linked, reduced dystrophin
D) Becker’s muscular dystrophy has an X-linked inheritance, but has a slower clinical progression than Duchenne. They both have the same gene location (Xp21), but patients with Becker’s muscular dystrophy have 20% to 80 %, or even normal quantities, of dystrophin.
Which of the following myopathies is not associated with cardiac abnormalities?
a. Becker’s muscular dystrophy (BMD)
b. Duchenne muscular dystrophy (DMD)
c. Facioscapulohumeral dystrophy (FSHD)
d. Limb-girdle muscular dystrophy (LGMD)
C) The presence of cardiac abnormalities in FSHD is rare. It is important to note that cardiomyopathy is seen prominently in Becker’s and Duchenne muscular dystrophy.
These patients have abnormalities in the dystrophin protein that is also present in myocardium and Purkinie fibers. ECG abnormalities can be seen, such as Q waves in lateral leads, elevated ST segments, poor R wave progression, and resting tachycardia.
Cardiomyopathy is seen in nearly all patients older than 18 years in Duchenne.
Cardiomyopathy may also be seen in Limb-girdle muscular dystrophy.
Cognition may be impaired in which of the following myopathies?
a. Becker’s muscular dystrophy (BMD)
b. Duchenne muscular dystrophy (DMD)
c. Facioscapulohumeral dystrophy (FSHD)
d. Limb-girdle muscular dystrophy (LGMD)
B) The dystrophin isomer is present in the brain. Since there is an absence of this dystrophin protein in DMD, there have been lower intelligence quotients seen in affected children. Mean IQ scores have been 1 to 1.5 standard deviations below the normal population. An increase in autism and obsessive-compulsive disorder is also seen in DMD patients.