Dr. Mike Lawlor's Proposed Muscle Biopsy Checklist

Comments are encouraged!!!!

Clinical History

1.  Gender of patient:    __male ___female

2.  Age at presentation:  _ _ years _ _ months

3.  Age at biopsy: _ _ years _ _ months

4.  Symptoms at presentation (check all that apply):

 Weakness

 Hypotonia

 Muscle pain

 Cardiac disease

 Central nervous system disease

 Respiratory difficulties

 Contractures

 Failure to thrive

 Others (see item 8)

5.  Elevated creatine kinase:  Yes  No  Unknown _______ Patient Value _________(Normal Range)

6.  Familial Inheritance:____None      ___Autosomal Recessive     ____Autosomal Dominant     ____X-linked

7.  EMG Findings: ____Not known        ____Myopathic              ____Neuropathic

8.  Other symptoms, signs, and lab data: ____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Muscle Biopsy Tissue Information

1.            Name of Muscle:___________________________________________________________________

2.            Size of tissue collected*:  ______  X  ______   X  ______ cm

3.            Date of tissue collection*:        __ __ / __ __ / __ __ __ __

                                                m  m     d   d     y   y   y   y

4.            Biopsy method:  Open         Needle

5.            Freezing or Fixation Used*?      Frozen:                   Amount: _____ mg     Not known

 Formalin-fixed:         Amount: _____ mg     Not known

 Paraffin-embedded: Amount: _____ mg     Not known      

 Epon-embedded:      Amount: _____ mg     Not known

Histological Findings in Muscle Biopsy or Autopsy specimens

1.       Which standard histochemical stains were used*? (choose all that apply)

 H and E                   Gomori trichrome      NADH         COX            SDH

 COX/SDH                PAS                        Oil Red O     ATPase 4.3  ATPase 4.6

 ATPase 9.4              Other, specify: __________________________________________________________________________________________________________________________________________________________________________________

2.       Which of the following diagnostic abnormalities were noted on histochemical stains (choose all that apply)*?

Fatty replacement                ___absent         ___mild             ___moderate                 ___severe

Endomysial fibrosis              ___absent         ___mild             ___moderate                 ___severe

Myofiber degeneration                      ___absent         ___mild             ___moderate                 ___severe

Necrosis                             ___absent         ___mild             ___moderate                 ___severe

Myophagocytosis                 ___absent         ___present in ____ fibers

Myofiber regeneration (Basophilic fibers)        ____absent       ___present in _____ fibers

Abnormalities of fiber type          ____absent       _____present

Specify*:      Type 1 predominance                       ______ % Type 1 fibers

 Type 2 predominance                 ______% Type 2 fibers

 Fiber type grouping (of both fiber types)

Hypertrophic fibers               ____absent       _____present in _____ fibers

Atrophy/Hypotrophy                   ____absent       _____present

Specify:       All fibers within the specimen          

 Subsets of fibers, leading to excessive variation in fiber size

Specify (choose all that apply):    Single fibers                         Groups of fibers      

                                     Type 1 fibers only     Type 2 fibers only

Perifascicular distribution

             Atrophic/hypotrophic fiber shape

 Angulated     Round    

Myopathy-associated pathological structures, specify:     

Central nuclei                _____absent      _____present

Specify estimated % of fibers (include eccentric nuclei): _____

            Internal nuclei                _____absent      _____present

Specify estimated % of fibers (if not quantified above): _____

Inclusion bodies             ____absent       ____present in _____ fibers

Rimmed vacuoles                      ____absent       ____present in _____ fibers

            Nemaline rods               ____absent       ____present

Specify:             Restricted to one fiber type, specify which: _____     

                                                 Nuclear rods present

Ragged red fibers                      ____absent       ____present in _____fibers

COX- negative fibers                  Estimated number ______

Strongly SDH-reactive blood vessels (SSV’s)                  _____absent      _____present

Central cores                 ____absent       ____present in _____ fibers

            Minicores                      ____absent       ____present in ____ fibers

            Core-like lesions            ____absent       ____present in ____ fibers

            Targetoid fibers              ____absent       ____present in ____ % of fibers

            Marked hypotrophy of type 1 fibers                      ____absent       ____present

Inflammation                 ___absent         ___mild             ___moderate                 ___severe

Specify:

 Distribution

 Perivascular

                               Evidence of vascular damage            Thrombi identified in blood vessels

                         Focal

 Diffuse

 Endomysial

 Perimysial

 Involving fascia

             Associated with myofiber damage

              Associated with non-necrotic myofiber

              Granulomas

                        Necrotizing   Non-necrotizing   Giant cells present    Foreign material present

             Inflammatory cells identified

                        Specify (choose all that apply):

                         Lymphocytes

                         Neutrophils

                         Macrophages

                         Eosinophils (as a prominent component)

                         Microorganisms identified, specify which: _________________________________________

Abnormal storage material

Specify:

                        Excessive glycogen                    ____absent      ____mild           ____severe

                        Excessive intracellular lipid         ____absent       ____mild           ____severe

Additional observations

____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

3.       Which immunohistochemical stains were used? (choose all that apply)

 Myosin immunohistochemistry (for fast and slow fibers)         

 Dystrophin panel

            Specify:

                        Dystrophin (DYS1)         ____absent       ____reduced      ____normal

                        Dystrophin (DYS2)         ____absent       ____reduced      ____normal

                        Dystrophin (DYS3)         ____absent       ____reduced      ____normal

                        Dystrophin (BMD Hotspot)         ____absent       ____reduced      ____normal

                        Spectrin                                    ____absent       ____reduced      ____normal

                        Utrophin                                    ____absent       ____normal       ____increased

                       

 Other stains for limb-girdle or congenital muscular dystrophy

            Specify:           

                        Laminin a2/Merosin                   ____absent       ____reduced      ____normal

                        Alpha dystroglycan (VIA)            ____absent       ____reduced      ____normal

                        Alpha dystroglycan (IIH)             ____absent       ____reduced      ____normal

                        Beta dystroglycan                      ____absent       ____reduced      ____normal

                        Alpha sarcoglycan                     ____absent       ____reduced      ____normal

                        Beta sarcoglycan                       ____absent       ____reduced      ____normal                  

Delta sarcoglycan                      ____absent       ____reduced      ____normal

                        Gamma sarcoglycan                  ____absent       ____reduced      ____normal

Dysferlin                                   ____absent       ____reduced      ____normal                  

Emerin                                      ____absent       ____reduced      ____normal

                        Collagen VI                               ____absent       ____reduced      ____normal

                        Caveolin 3                                 ____absent       ____reduced      ____normal

                        Desmin                                     ____absent       ____reduced      ____normal

                        Integrin a7                                ____absent       ____reduced      ____normal

                        nNOS                                       ____absent       ____reduced      ____normal

                       

 Inflammatory myopathy panel

                        CD4                                         ____absent       ____present in ___ % of lymphocytes

                        CD8                                         ____absent       ____present in ___ % of lymphocytes

                        CD20                                        ____absent       ____present in ___ % of lymphocytes

                        CD45                                        ____absent       ____present in ____% of mononuclear cells        

CD68                                        ____absent       ____present in ____% of mononuclear cells        

C5b-9                                       ____absent       ____present on endomysial capillary walls

Major Histocompatability Complex          ____absent     ____sarcolemmal       ____diffuse

4.        Additional immunohistochemical/immunofluorescence assays performed: __________________________________________________________________________________

5.       Other abnormalities noted on immunohistochemistry:  __________________________________

Epon-Embedded Tissue/Electron Microscopy (Muscle Biopsy/Autopsy Specimens)

1.       Abnormalities seen on:             Light microscopy (Toluidine blue staining)       Electron microscopy

 Both – Light microscopy and Electron microscopy

2.       Abnormalities noted in:            Contractile apparatus

                                                 Sarcotubular organization

                                                 Mitochondria, specify (choose all that apply):

 Abnormal shape       

 Abnormal numbers

                                                                         Abnormal location   

                                                                         Abnormal architecture

3.       Describe any pathological inclusions noted:     N/A _________________________________________________________________________________________

_________________________________________________________________________________________

4.       Describe any abnormal storage material identified:       N/A _________________________________________________________________________________________

_________________________________________________________________________________________

Interpretation:

Comment:

Best Post of December 2012: "the NFL is a breeding ground for mental illness" -- Former Denver Bronco Nate Jackson

The next in our "Best of the Month" series is from December 4, 2012:

Today, a friend forwarded me this opinion piece about the murder-suicide of NFL linebacker Jovan Belcher. I responded that I blogged about such cases before, and I didn't intend to write yet another blog post about chronic traumatic encephalopathy. I felt as though lethal violence among football players is happening so often now, it's not even worth yet another post. But, the fact that the violence has reached this level of banality is in itself worthy of comment. Don't worry, though, the next time an NFL player commits homicide or suicide, I promise not to write about it.

Mutations in COQ2 in Familial and Sporadic Multiple System Atrophy

Researchers from the Multiple System Atrophy (MSA) Research Collaborative in Japan just published online in the New England Journal of Medicine findings providing evidence that functionally impaired variants of the COQ2 gene (involved in the biosynthetic pathway for coenzyme Q10) are associated with an increased risk of developing MSA. This group previously identified multiplex families with MSA, indicating a genetic component in a disease that had previously been considered a non-genetic disorder.

Best Post of November 2012: Photos reveal unique features of Einstein's cerebral cortex

The next in our "Best of the Month" series is from November 21, 2012:

Photographs taken shortly after his death, but never before analyzed in detail, have now revealed that Einstein’s brain had several unusual features, providing clues about the neural basis of his extraordinary mental abilities.

Nature.com reports that, while doing Einstein's autopsy, the pathologist Thomas Harvey removed the physicist's brain and preserved it in formalin. He then took dozens of black and white photographs of it before it was cut up into 240 blocks. Now, anthropologist Dean Falk of Florida State University in Tallahassee and her colleagues have obtained 12 of Harvey’s original photographs from the National Museum of Health and Medicine in Silver Spring, Maryland, analyzed them, and compared the patterns of convoluted ridges and furrows with those of 85 brains described in other studies. Many of the photographs were taken from unusual angles, and show structures that were not visible in photographs that have been studied previously. The analysis was recently published in the journal Brain. The most striking observation, says Falk, was “the complexity and pattern of convolutions on certain parts of Einstein's cerebral cortex”, especially in the prefrontal cortex, and also parietal lobes and visual cortex.