MND Flashcards
(131 cards)
1
Q
• A group of progressive degenerative disorders of the motor neurons in the spinal cord, brainstem, motor cortex, manifest clinically by muscular weakness, atrophy, and corticospinal signs in varying combinations
A
Motor Neuron Disease
2
Q
Motor Neuron Disease manifested by
A
muscular weakness, atrophy, and corticospinal signs in varying combinations
3
Q
MND
Disorders that predominantly or exclusively affect the
A
UMN
LMN
Both
4
Q
T or F
Sensory neurons are spared
A
True
5
Q
Causes of MND
A
Hereditary
Sporadic
6
Q
Spectrum of MND
LMN
A
Flail leg syndrome
Flail arm syndrome
Progressive muscular atrophy
7
Q
Spectrum of MND
Both
A
Classical ALS
Limb onset, bulbar onset
8
Q
Spectrum of MND
UMN
A
Isolated bulbar palsy
Hemiplegic ALS (Mills)
Primary Lateral Sclerosis
9
Q
LMN Symptoms
A
Cramps
Fasciculations
10
Q
LMN Signs
A
• Fasciculations
• Muscle atrophy
• Muscle weakness
• Hyporeflexia/absent reflexes
11
Q
UMN Symptoms
A
• Stiffness/slow movement
• Clonus, Spasms
• +/- Emotional lability
12
Q
Inc muscle tone
A
Umn
13
Q
Slow out of proportion to weakness
A
Umn
14
Q
No fasciculation
A
Umn
15
Q
+ weakness
A
Umn
16
Q
+- muscle wasting
A
Umn
17
Q
Hyperactive reflexes
A
Umn
18
Q
+ babinski
A
Umn
19
Q
Dec muscle tone
A
Lmn
20
Q
UMN Signs
A
• Spasticity
• Hyperreflexia
• Preserved reflex in wasted limb
21
Q
Slow d/t weakness
A
Lmn
22
Q
++ muscle wasting
A
Lmn
23
Q
Areflexia
A
Lmn
24
Q
No babinski
A
Lmn
25
Pseudobulbar affect
Umn
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Spasticity
Umn
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Extensor plantar reflexes
Umn
28
Confirmation of LMN dysfunction in patients with ALS and LMN disorders
Identification of focal conduction blocks in patients with multifocal motor neuropathy
Detection of sensory nerve involvement in peripheral neuropathies
Nerve conduction/ electromyography
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Detection of corticospinal tract abnormalities in ALS; however, lesions not always seen Identification of structural abnormalities affecting brain, spine, or both
MRI of the brain and the spine
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Detection or confirmation of UMN degeneration when UMN signs not clearly present
Spectroscopy
31
Detection of inflammatory process
Elevated (SF protein may indicate polyneuropathy, polyradiculopathy, or lymphoma
Lumbar puncture
32
ALS meaning
Amyotrophic Lateral Sclerosis
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Amyotrophic Lateral Sclerosis aka
Lou Gehrig’s Disease
34
Most common MND in adults
Amyotrophic Lateral Sclerosis (ALS)
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ALS onset
• 10% with onset before age 40
• 5% with onset before age 30 - hereditary MND
Progressive, insidous
36
++ weakness
Lmn
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ALS risk
M>F
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ALS DEATH
• Most patients die within 3-5 years of onset of symptoms
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ALS
Sx and symp
Subacute to chronic progressive weakness, symmetric at onset
• 30% upper extremity
• 35% lower limb
• 30% bulbar
• UMN + LMN signs and symptoms
No, asymmetric
40
Als
• Preservation of EOMs
Yes
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Also bladder and bowel dysfunction
No, intact
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Als
• Absence of cognitive and sensory changes if no associated FTD (10%)
Yes
43
Majority cause of ALS
Sporadic of unknown cause
44
Als pathobiology
presence of intraneuronal inclusions
Ubiquitinated Skein-like inclusion
Axonal swelling and spheroids
Motor Neuron degeneration
45
Als manifestations
Atrophy and fasciculations of tongue
• Dysarthria before dysphagia
• Lateral borders of tongue waste first and symmetrically
• Spasticity, spastic gait
• Babinski, clonus, Hoffman
• Clumsiness
• Slow rapid alternating movements
• Facial weakness and wasting especially in mentalis
• Pseudobulbar palsy
Split hands
• Progressive painless weakness with prominent atrophy and fasciculations
• Overactive reflex with Hoffman sign in arms that are weak, wasted and with fasciculations
• Muscle cramps - hypersensitivity of denervated muscles
• Weight loss - muscle wasting and dysphagia
• Respiratory impairment - diaphragm and paresis of intercostal muscles; early or late
• Pain may occur later when limbs are immobile due to spasticity and contractures
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hypersensitivity of denervated muscles
Muscle cramps
47
muscle wasting and dysphagia
Weight loss
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diaphragm and paresis of intercostal muscles; early or late
Respiratory impairment
49
preferential atrophy of the thenar (APB, FDI) with relative preservation if the hypothenar muscles; specific and early feature of ALS
Split hand
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Criteria for ALS Dx
Revised El Escorial Criteria for Diagnosis of ALS
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Upper and lower motor neuron signs in 3 regions
Definite ALS
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Upper and lower motor neuron signs in at least 2 regions, with upper motor neuron signs rostral to lower motor neuron signs
Probable ALS
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Upper and lower motor neuron signs in at least 2 regions, with upper motor neuron signs rostral to lower motor neuron signs
Possible ALS
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Lower motor neuron signs only, in 2 or more regions
Suspected ALS
56
Upper and lower motor neuron degeneration
Amyotrophic lateral sclerosis (ALS)
57
Purely lower motor neuron involvement
Progressive muscular atrophy (PMA)
58
Purely upper motor neuron involvement
Primary lateral sclerosis (PLS)
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Bulbar symptoms only or bulbar-onset ALS
Progressive bulbar palsy
60
Lower motor neuron predominant, one arm
Monomelic muscular atrophy
61
Lower motor neuron predominant, both arms
Bibrachial amyotrophy
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<8% of MND
Progressive Muscular Atrophy
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Pure LMN form of MND
Progressive Muscular Atrophy
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Male
• Asymmetrical wasting and weakness, often in the legs that later coalesce to involve 4-limb LMN
Progressive Muscular Atrophy
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<3 MND
Primary Lateral Sclerosis
66
Progressive MND with pure UMN problem
Primary Lateral Sclerosis
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• Slowly progressive spastic quadriparesis
Spasticity, gait dysfunction, spastic dysarthria, hyperreflexia
Burden of disability is high
• Consistent with good survival
Primary Lateral Sclerosis
68
Primary Lateral Sclerosis onset
40
69
Primary Lateral Sclerosis observation
4 yrs
70
MND selectively affecting bulbar muscles
• Dysarthria, dysphagia
Progressive Bulbar Palsy
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Progressive Bulbar Palsy onset
• Most are bulbar-onset ALS - rapid progression to limb weakness and decreased survival
• Females, >65 yo, typically retain normal limb strength despite progression to anarthria within a year
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UMN features (slow spastic tongue with jaw jerk) predominate
Progressive Bulbar palsy
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UMN features (slow spastic tongue with jaw jerk) predominate
Progressive Bulbar Palsy
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Focal MND restricted to 1 limb, LMN predominant
• Hirayama syndrome, monomelic amyotrophy, monomelic ALS, benign focal atrophy
Monomelic Muscular Atrophy
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Monomelic Muscular Atrophy
Onset and risk factors
• M>F (10x)
• Onset: 20yo
• Common in southeast Asia (Japan and India)
76
Monomelic Muscular Atrophy involvement
arm C7-T1 innervation
77
Monomelic Muscular Atrophy
Progression
slowly then stabilizes
78
Bibrachial Amyotrophy aka
Brachial diplegia
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• LMN predominant with some UMN signs
Bibrachial Amyotrophy
80
Restricted to both arms
• Bilateral weakness and wasting of proximal upper limb
• Arm posture is typically pronated and arms are dangling
• Man-in-a barrel
• May be associated with dropped head
Bibrachial Amyotrophy
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Bibrachial Amyotrophy
Risk and progression
• M>F (8-9:1)
• Slower progression
• Respiratory muscles affected late in disease
• Survival 5-7 years
82
Kennedy disease aka
X-Linked Recessive Spinobulbar Muscular Atrophy
83
Kennedy disease gene
Xq 11-12
84
site of androgen receptor
Xq 11-12
85
Xq 11-12 mutation
expansion of CAG repeat
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Kennedy Disease onset and prevalence
• Onset 3rd to 5th decade
• Prevalence 1/40,000
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Prominence in Kennedy disease
LMN dysfunction in limb (more prominent proximally) and facial muscles
• Dysarthria, dysphagia with prominent tongue and mentalis fasciculations
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Course of Kennedy disease
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Course of Kennedy disease
• Slow course with limb weakness delayed for years
90
Manifestation of Kennedy disease
• LMN dysfunction in limb (more prominent proximally) and facial muscles
• Dysarthria, dysphagia with prominent tongue and mentalis fasciculations
• Slow course with limb weakness delayed for years
• Large fiber sensory peripheral neuropathy
• Gynecomastia and impotence
91
Hereditary Spastic Paraparesis
Link
AD, AR, X-linked
92
• Insidiously progressive gait disturbance
• Variable age of onset
Hereditary Spastic Paraparesis
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Manifestation of Hereditary Spastic Paraparesis
Uncomplicated or pure
• Spastic leg weakness with hyperreflexia, Babinski
• Urinary urgency, frequency or hesitance
• Mild loss of vibration sense on legs
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Manifestation of complicated hsp
• Spastic paraparesis with neurologic abnormalities (optic atrophy, retinopathy, seizures, MR, dementia, extrapyramidal abnormalities, peripheral neuropathy)
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Hsp treatment
Symptomatic
96
Critical to confirming lower motor neuron involvement in ALS
• Rule out mimics
CMAP & EMG
97
Camp results
normal or low amplitude
• Normal sensory responses
98
Emg results
active denervation (fibrillation and fasciculations) and chronic denervation in 3 regions
99
Other diagnostic tests
• Neuroimaging - rule out brain and spine disorders
• CSF analysis
• Blood tests
• Genetic testing
• Muscle biopsy
100
Prevent nerve cell death by blocking stress signals
• Approved 2022
• Relyvrio - combination of sodium phenylbutyrate and taurursodiol
101
Other formulations of riluzole
• Riglutik (thickened riluzole) - approved 2018
• Exservan (riluzole oral film) - approved 2019
102
• Treatment of pseudobulbar affect
• Approved 2011
• Nuedexta (dextromethorphan and quinidine sulfate)
103
Autosomal recessive MND
SMN (survival motor neuron) gene mutation
Spinal Muscular Atrophy (SMA)
104
Subacute weakness with variable age of onset
• LMN dysfunction
• Absence of cognitive and sensory changes
Spinal Muscular Atrophy (SMA)
105
SMNI mutation at chromosome
5q11 with resultant reduction of SMN
protein levels
106
required for assembly of spliceosomal small nuclear ribonucleoproteins which are involved in mRNA processing
SMN
107
SMA Treatment
symptomatic management
108
Spinal muscle atrophy course
Mutation in smn1 gene
Deficiency in smn protein leads to splicing defects in motor neuron
Loss of motor neurons in the anterior horns of the spinal cord prevents signalling between the brain and skeletal muscles
Progressive muscle atrophy
109
near identical to SMN 1
• Produces small amounts of residual protein
• Obviating the inevitable lethality associated with complete loss of
SMN protein
SMN2
110
T or f
Disease severity is not proportional to residual SMN
levels, which are a function of the SMN 2 copy
Is proportional
111
Begins within first 6 months of life
• Frequent cause of floppy infant syndrome
• Never sit independently
• Death before age 2 if no respiratory or nutritional support
• 2 SMN 2 copies
SMA I (infantile or Werdnig Hoffman disease)
112
• Starts between ages 6-18 months
• Develop ability to sit unsupported
• Never walk
• Complications: respiratory insufficiency and scoliosis
• Normal or slightly reduced life expectancy
• 3 SMN 2 copies
SMA I| (intermediate or chronic infantile disease or Dubowitz disease)
113
• After age 18 months
• Type Ill a: able to walk before age 3
• Type III b: able to walk after age 3
• Manifest as difficulty climbing stairs or impaired walking
• Normal life expectancy
• Rare serious dysphagia and respiratory compromise
• 3-4 SMN 2 copies
• SMA III (Kugelberg-Welander or chronic juvenile disease)
114
able to walk before age 3
Type Ill a:
115
able to walk after age 3
Type III b:
116
Onset adulthood
• Only 50% have SMN mutations
• AD, AR, X-linked
• SMN IV
117
Spinal Muscular Atrophy (SMA)
Clinical manifestation
EOMs spared
• Facial weakness mild or absent
• With tongue fasciculations
• Postural tremor
• Respiratory muscles affected
• Weak axial muscles which can lead to scoliosis
118
SMA Dx and treatment
Diagnosis: genetic testing
• Treatment:
• Supportive
• Physical therapy
• Reduce risk of infection
119
Other SMA not related to chromosome 5
Fazio-Londe Syndrome
• Scapuloperoneal and Facioscapulohumeral forms of SMA
• Childhood SMA with known biochemical abnormality
120
• Selective dysarthria and dysphagia begin in late childhood or adolescence
• Tongue atrophy with fasciculations
• May also affect limbs and respiration but occurs later
• Fazio-Londe Syndrome
121
Poliomyelitis cause
enterovirus from Picornaviridae family
122
Poliomyelitis transmission
orofecal route (main) and pharyngeal spread
• Secreted in saliva and feces
123
Flu-like illness
Direct passage through BBB, or retrograde axonal transport from muscle to SC and brain
• LE>UE
• Proximal
• Loss of reflexes
• Normal sensation
Poliomyelitis
Acute Illness
124
high fever with pharyngitis, myalgia, anorexia, N&V, headache, neck stiffness
• Meningitic phase
125
- myalgia and severe muscle spasms, with subsequent development of asymmetric, flaccid weakness which becomes maximal after 48 hrs
Spinal poliomyelitis
126
Poliomyelitis
Diagnosis
• CSF - increased protein and pleocytosis; normal glucose
• Virus isolation:
• Nasopharynx - 1st week
• Stool
• PCR for identification of virus
127
• 1956
• Trivalent inactivated polio vaccine (IPV)
• IM
• Stimulates secretion of IgM, IgG, IgA but not secretory IgA
Jonas Salk
128
• 1962
• Trivalent live oral polio vaccine (OPV)
• Stimulates secretory IgA as well
Albert Sabin
129
Factors Associated with the Development of Post Polio Syndrome
Onset of functional deterioration after a prolonged period of stability
Young onset of acute polio
Severe limb, bulbar or respiratory involvement during acute polio
Incomplete recovery with residual disability
Greater physical activity during intervening years
Development of new symptoms or impairment associated with intercurrent events
Development of symptoms including:
Pain in joints, bones and muscles
Fatigue
Cramps, fasciculation
Wasting, weakness
Deterioration in functional abilities:
Activities of daily living
Mobility
Upper limb function
Respiratory function
130
Post polio syndrome tx
Specific treatment of increasing impairment
• Enable patient to cope with new disabilities
131
• New neuromuscular symptoms that some patients develop 15 years after reaching maximum recovery from acute paralytic poliomyelitis; unrelated to orthopedic, neurological, psychiatric or systemic illness
• Insidious onset of progressive impairment or functional deterioration
• Weakness usually in previously affected limb but may also occur as a result of extra load on unaffected limb
Post polio syndrome
