Sandbox Myopathy: Difference between revisions

Jump to navigation Jump to search
No edit summary
No edit summary
Line 25: Line 25:
==Differentiating Various Muscle Weakness==
==Differentiating Various Muscle Weakness==
{| class="wikitable"
{| class="wikitable"
! rowspan="3" |Disease
! rowspan="2" |Disease
! colspan="9" |Symptoms
! colspan="9" |Symptoms
! rowspan="3" |History
! rowspan="2" |History
! rowspan="3" |Physical
! rowspan="2" |Physical
Examination  
Examination  
! colspan="4" |Diagnosis
! colspan="4" |Diagnosis
|-
|-
! rowspan="2" |Age of onset
!Age of onset
! colspan="2" |Muscle weakness
! colspan="2" |Muscle weakness
! rowspan="2" |Fever
!Fever
! rowspan="2" |Muscle pain
!Myalgia
! rowspan="2" |Gait abnormality
!Gait abnormality
! rowspan="2" |Neuropathy
!Neuropathy
! rowspan="2" |Myoglobinuria
!Myoglobinuria
! rowspan="2" |Other features
!Other features
! rowspan="2" |Laboratory Findings
!Laboratory Findings
! rowspan="2" |Creatine Kinase
!Creatine Kinase
! rowspan="2" |Muscle Biopsy
!Muscle Biopsy
! rowspan="2" |Electromyogram
!Electromyogram
|-
!Proximal
!DIstal
|-
|-
! colspan="16" |Medications
! colspan="16" |Medications
Line 53: Line 50:
|
|
* Variable
* Variable
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 83: Line 80:
|
|
* 60+
* 60+
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 110: Line 107:
|
|
* Variable
* Variable
|     '''+'''
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 141: Line 138:
|
|
* 25 -45
* 25 -45
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 181: Line 178:
|
|
* 30-50 years
* 30-50 years
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 217: Line 214:
|
|
* 50
* 50
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>+</nowiki>
* Proximal
 
* Distal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 245: Line 244:
|
|
* 40
* 40
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 274: Line 273:
|
|
* >55
* >55
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
| -
| -
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 300: Line 299:
|
|
* 45 
* 45 
| +
| colspan="2" |
| -
* Proximal
| +
| +
| +
| +
Line 335: Line 334:
* 40s-50s
* 40s-50s
* Can affect childreen  
* Can affect childreen  
|<nowiki>+</nowiki>
| colspan="2" |
| -
* Proximal
| +
| +
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 367: Line 366:
|
|
* > 18 years  
* > 18 years  
|<nowiki>+</nowiki>
| colspan="2" |
| -
* Proximal
| +
| +
| +
| +
Line 389: Line 388:
|
|
* 50s  
* 50s  
|<nowiki>+</nowiki>
| colspan="2" |
| +
* Proximal
* Distal
|
|
|
|
Line 408: Line 408:
|
|
* 40-50s  
* 40-50s  
|
| colspan="2" |
+
* Generalized
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
| -
| -
Line 438: Line 437:
|
|
* 50s
* 50s
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Diffuse
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
| +
| +
Line 482: Line 481:
|Becker muscular dystrophy
|Becker muscular dystrophy
|<13yrs
|<13yrs
|<nowiki>+</nowiki>
| colspan="2" |Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 508: Line 506:
|Duchenne muscular dystrophy
|Duchenne muscular dystrophy
|<13 yrs
|<13 yrs
| +
| colspan="2" | Proximal
| -
| -
| -
| -
| -
Line 536: Line 533:
|Limb-girdle muscular dystrophies
|Limb-girdle muscular dystrophies
|<15 yrs
|<15 yrs
|<nowiki>+</nowiki>
| colspan="2" |Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 566: Line 562:
|Myotonic dystrophy type 1
|Myotonic dystrophy type 1
|
|
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>+</nowiki>
* Proximal
 
* Distal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 593: Line 591:
|Lyme disease
|Lyme disease
|Variable
|Variable
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
| +
| +
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 623: Line 621:
|Infulenza
|Infulenza
|Variable
|Variable
|<nowiki>-</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Negative
| +
| +
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 651: Line 649:
|Polio
|Polio
|<5 yrs
|<5 yrs
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
| -
| -
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 681: Line 679:
|Syphilis
|Syphilis
|Variable
|Variable
|<nowiki>-</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Negative
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 714: Line 712:
|Pyomyositis
|Pyomyositis
|Variable
|Variable
|<nowiki>+/-</nowiki>
| colspan="2" |
|<nowiki>+/-</nowiki>
* Proximal
* Distal
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
Line 744: Line 743:
|ALS
|ALS
|
|
|
| colspan="2" |
|
|
|
|
|
Line 766: Line 764:
|
|
* >65
* >65
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>+</nowiki>
* Proximal
* Distal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 793: Line 792:
|
|
* 18  -350
* 18  -350
| -
| colspan="2" |
|<nowiki>+</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 837: Line 836:
|
|
* Variable
* Variable
|<nowiki>-</nowiki>
| colspan="2" |
|<nowiki>+</nowiki>
* Distal
|
|
|
|
Line 856: Line 855:
|
|
* Variable
* Variable
|<nowiki>+</nowiki>
| colspan="2" |
(the muscles closer to the trunk)
* Distal
| -
|
|
|
|
Line 876: Line 874:
|
|
* Variable
* Variable
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>+</nowiki>
* Proximal
|
|
|
|
Line 922: Line 920:
|
|
* Variable
* Variable
|<nowiki>+</nowiki>
| colspan="2" |
|<nowiki>-</nowiki>
* Proximal
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
Line 951: Line 949:
* Normal
* Normal
|-
|-
|Mitochondrial
|
|
|
|
Line 956: Line 955:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|}
{| class="wikitable"
!
! colspan="9" |Symptoms
!
|-
!
! colspan="5" |Positive
! colspan="4" |Neagtative
!
|-
!
!Myalgias
!Cramps
!Contractures
!Myotonia
!Myoglobinuria
!Weakness
!Exercise intolerance
!Muscle atrophy
!
!
|-
|Toxic/drug-induced myopathies 
| +
|
|
|
|
|
|
|
|
|
|-
|Hypothyroid myopathy
| +
|
|
|
|
|
|
|
|
|
|-
|
|
|
|

Revision as of 20:46, 7 April 2018


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Flow chart

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Objective Muscle weakness
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malignancy
Arthralgia
Anemia
Firbomyalgia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generalized
 
 
 
 
 
 
 
 
 
 
 
 
 
Localized
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myasthenia gravis
Periodic paralysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Asymmetric
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symmetric
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cerebrovascular accidents
Demyleinating disorders
Atrophy
Mononeuropathy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specific pattern
 
 
 
 
 
 
 
Specific pattern
 
 
 
 
 
 
 
Proximal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hereditary neuropathy
Muscular dystrophy
 
 
 
 
 
 
 
Myoapthy
Duchenne muscular dystrophy
 
 
 
 
 
 
 
Motor neuron disease
Peripheral neuropathy
 
 
 

Differentiating Various Muscle Weakness

Disease Symptoms History Physical

Examination

Diagnosis
Age of onset Muscle weakness Fever Myalgia Gait abnormality Neuropathy Myoglobinuria Other features Laboratory Findings Creatine Kinase Muscle Biopsy Electromyogram
Medications
Corticosteroids
  • Variable
  • Proximal
- + - - -
  • + History of medications
  • Facial and sphincter muscles usually are spared
- - -
Statins
  • 60+
  • Proximal
- + - - -/+(rhabdomyolysis)
  • N/A
  • Positive medication history
  • Tenderness
  • Muscle aches
  • ↑↑ liver enzymes
  • ↑↑
  • Necrosis
  • Degeneration, and regeneration of fibers
  • Phagocytic infiltration
-
Alcohol
  • Variable
  • Proximal
- - + +/- -
  • Swelling
  • Tender
  • Erythema and induration
  • Alcohol intoxication
  • Change in mental status
  • Telangiectasia
  • Peripheral neuropathy
  •  nonspecific and are normal in many patients
  • Normal or ↑↑
  • Normal
  • Normal
Endocrine
Cushing's disease
  • 25 -45
  • Proximal
- - - - -
  • Decreased libido
  • Obesity/weight gain
  • Plethora
  • Round face
  • Menstrual changes
  • Hirsutism
  • Hypertension
  • Ecchymoses
  • Lethargy, depression
  • Dorsal fat pad
  • Abnormal glucose tolerance
  • N/A
  • Facial and sphincter muscles usually are spared
  • Overweight
  • Straie
  • Moon face
  • HTN
  • Hyperpigmentation
Normal
  • Atrophy of type 2 muscle fibers, especially type 2B
Normal
Adrenal insufficiency
  • 30-50 years
  • Proximal
- - - - -
  • Signs of glucocorticoid, mineralocorticoid, and, androgen deficiency.
  • Hypotension 
  • Hyperpigmentation 
  • Auricular-cartilage calcification 
  • Vitiligo
  • Electrolyte abnormalities
  • Hypoglycemia 
  • Normal
  • Normal
  • Normal
Hyperaldosteronism with myopathy 
  • 50
  • Proximal
  • Distal
- - - - +

Rhabdomyolysis

  • Palpitations
  • Hypertension
  • Episodes of heart beats
  • Hyperpigmentation
  • Hypokalemia
  • Normal
  • Normal
  • Normal
Hyperthyroidism
  • 40
  • Proximal
- - - - +
  • Signs of hyperthyroidism
  • Sweating
  • Tremor'
  • H/o of weight loss
  • Sweating
  • Tremor'
  • Swelling on neck examination
  • Decreased TSH
  • ↑↑
  • Non specific
  • Myotonic
Hypothyroidism
  • >55
  • Proximal
- + - - + Rhabdomyolysis
  •  Signs of hypothyroidism
  • H/o weight gain
  • Myoedema 
  • Muscle pseudohypertrophy
  • Increased TSH
  • ↑↑
  • Nonspecific 
  • Normal
Diabetic infraction
  • 45 
  • Proximal
+ + - + -
  • Cramps
  • Sudden onset of pain
  • Anterior thigh muscles are most commonly involved
  • H/O long standing diabetes
  • Swelling
  • Tenderness
  • Elevation of the erythrocyte sedimentation rate
  • Leukocytosis
  • Normal
  • Necrosis
  • Edema
  • Normal
Inflammatory / Rheumatologic
Dermatomyositis[1]
  • 40s-50s
  • Can affect childreen
  • Proximal
+ + - - -
  • Rash
  • Dyspnea
  • Weight loss
  • Cough
  • Heliotrope rash on face and hands
  • Telangectasia
  • Erythema
  • Mechanic's hands
  • Gottron's sign ( violaceous scaly eruption )
  • ↑↑ ESR
  • ↑↑ CRP
  • ↑↑
  • Perimysial mononuclear infiltrate
  • Muscle inflammation and damage
Polymyositis[2]
  • > 18 years
  • Proximal
+ + - - -
  • Similar to dermatomyositis without mucous and skin involvement
  • N/A
  • N/A
  • ↑↑
  • Endomysial mononuclear infiltrate
  • Patchy necrosis
Inclusion body myositis[3]
  • 50s
  • Proximal
  • Distal
  • ↑↑
Fibomyalgia
  • 40-50s
  • Generalized
- - - ++ -
  • Anxiety or depression features
  • Fatigue
  • Sleep disturbance
  • Numbness
  • Muscle spasms
  • History of depressive disorder
  • Tenderness in the soft tissue anatomical location
  • Normal
  • Normal
  • Normal
  • Normal
Polymyalgia Rheumatica[4]
  • 50s
  • Diffuse
+ + - - -
  • Weight loss
  • History of joints stiffness which is worse in the morning
  • Restricted shoulder motion
  • ↑ CRP
  • ↑ ESR
  • Normal
  • Normal
  • Normal
Idiopathic myopathy
Genetic
Becker muscular dystrophy <13yrs Proximal - - + - -
  • Milder form of Duchenne
  • Growth delay
  • Age of onset of symptoms is much delayed than duchenne
  • ↑↑
    • Muscle fibril degeneration, regeneration
    • Isolated fiber hypertrophy
    • Muscle replacement with fat and connective tissue
  • Myopathic changes
Duchenne muscular dystrophy <13 yrs Proximal - - + - -
  • Calf psedohypertrophy
  • Cardiomyopathy
  • Kyphoscoliosis
  • Cognitive impairment
  • Early onset
  • +Grower sign
  • ↑↑
Limb-girdle muscular dystrophies <15 yrs Proximal - + + - -
  • Calf hypertrophy
  • Scapular winging
  • Cardiomyopathy
  • Cardiac arrhythmias
  • Respiratory muscle weakness
  • Autosomal dominant
  • LMNA gene
  • CAV3 gene
  • ↑↑
  • -
Myotonic dystrophy type 1
  • Proximal
  • Distal
- - + - -
  • Myotonia
  • Cataracts
  • Diabetes mellitus
  • Frontal balding
  • Cardiac arrhythmias
  • Cholecystitis
  • Pregnancy
  • Eyelid ptosis
Infectious
Lyme disease Variable
  • Proximal
+ + +/- + -
  • + Tick bite
  • Hiking/Tip
  • Clinical diagnosis
  • +Serology
  • -
  • -
  • -
Infulenza Variable
  • Negative
+ + + - +
  • Fever
  • Malaise
  • Rhinorrhea
  • Muscle pain worse with movement
  • Muscle weakness, tenderness, and swelling.
  • ↑↑ Liver enzymes
  • +PCR
  • ↑↑
  • -
  • -
Polio <5 yrs
  • Proximal
- - + + -
  • Isolation from pharyngealsecretions, CSF
  • +Serology
  • -
  • -
  • Neurological pattern
Syphilis Variable
  • Negative
- - + + -
  • Chancre
  • Lymphadenopathy
  • Condylomata lata
  • Neuro syphilis
  • Cardiovascular syphilis
  • History of risk factors (MSM, unprotected sex, multiple sex partners)
  • Darkfield examinations
  • VDRL
  • RPR
  • FTA-ABS
  • -
  • -
  • -
Pyomyositis Variable
  • Proximal
  • Distal
+ + - - -
  • Fever
  • Malaise
  • Psoas abscess
  • Immunocopmprimised
    • Muscles are painful, swollen, tender, and indurated.
    • Depending on the site of involvement, it may mimic appendicitis (psoas muscle), septic arthritis of the hip (iliacus muscle), or epidural abscess (piriformis muscle).
  • Leukocytosis
  • Elevated ESR
  • -
  • -
  • -
Neurologic
ALS
  • Both upper and lower motor neuron signs 
  • Normal
  • Nonspecific findings of chronic denervation with reinnervation
  • Neuropathic
Stroke
  • >65
  • Proximal
  • Distal
- - + + -
  • Dysphagia
  • Unilateral/Bilateral weakness
  • H/o HTN, dyslipedemia DM
  • Weakness of the involved arm
  • Normal
  • Normal
  • Neuropathic
GBS
  • 18 -350
  • Proximal
- - + - -
  • Ascending paralysis
  • Precedes a gastrointestinal disease
  • Weakness of lower extremities followed by upper extremities
  • Cytologic albumin ratio
  • Normal
  • Normal
  • Neuropathic
Multiple Sclerosis
Neuro-muscular
Botulisim
  • Variable
  • Distal
  • H/O Food exposure and air
Lambert-Eaton myaes
  • Variable
  • Distal
  • Weakness is often relieved temporarily after exertion or physical exercise.
Myasthenia gravis
  • Variable
  • Proximal
  • Ocular
  • Bulbar 
  • Limb weakness
  • Isolated neck, limbs and respiratory weakness
Paraneoplastic
Metabolic
Glycogen storage disease
  • Variable
  • Proximal
- - - - -
  • AR
  • Faituge
  • Hypoglycemia
  • Exercise intolerance
  • Hypotonia
  • Hepatomeagly
  • Lactic acidosis
  • Elevated liver enzymes
  • ↑↑
  • Normal
  • Normal
Mitochondrial
Symptoms
Positive Neagtative
Myalgias Cramps Contractures Myotonia Myoglobinuria Weakness Exercise intolerance Muscle atrophy
Toxic/drug-induced myopathies  +
Hypothyroid myopathy +
  1. Dalakas MC (1991). "Polymyositis, dermatomyositis and inclusion-body myositis". N Engl J Med. 325 (21): 1487–98. doi:10.1056/NEJM199111213252107. PMID 1658649.
  2. Dalakas MC (1991). "Polymyositis, dermatomyositis and inclusion-body myositis". N Engl J Med. 325 (21): 1487–98. doi:10.1056/NEJM199111213252107. PMID 1658649.
  3. Dalakas MC (1991). "Polymyositis, dermatomyositis and inclusion-body myositis". N Engl J Med. 325 (21): 1487–98. doi:10.1056/NEJM199111213252107. PMID 1658649.
  4. Myklebust G, Gran JT (1996). "A prospective study of 287 patients with polymyalgia rheumatica and temporal arteritis: clinical and laboratory manifestations at onset of disease and at the time of diagnosis". Br J Rheumatol. 35 (11): 1161–8. PMID 8948307.