פרק 45 chapter 45 disease of muscle Flashcards
איזה מהגורמים הבאים מחמיר מיוטוניה אצל חולי myotonic
dystrophy
א. קור
ב. מאמץ פיזי
ג. טיפול בדיפניל הידנטואין
ד. טיפול במשתנים
ה. זיהום
א. קור
Myotonic Dystrophies:
DM1 – most common adult muscular dystrophy. AD with high penetrance CTG repeat, special topography of muscle atrophy, associated myotonia, dystrophic changes in nonmuscular tissue – lens of eye, testicle, skin, esophagus, heart. Certain muscles – levator palpabrae, facial, masseter, sternocleidomastoid, forearm and hands,anterior tibial muscles involved. Trinucleotide repeat CTG (normal 5-30 repeats , in dystrophy 50-2000) with anticipation correlating with severity. Repeat does not code form protein (intron)
4 features: 1. specific distribution – face, ptosis, limbs. 2. cardiac autonomic features 3. myotonia 4. dystrophic changes in non-muscular tissue – optic atrophy, testicular atrophy.
mor about DM1 – ‘ Hatchet face’ facial weakness and ptosis, atrophy of small muscles of hand and extensor muscles of forearm. Narrowing of lower half of face. Swan neck – due to weakness of Sternocleidomastoid, foot drop due to weakness of anterior tibial. Weak hypophonic voice. No contractures, patient confined to wheelchair within 15-20yrs of start. Myotonia – delayed relaxation after strong voluntary contraction. May be associated with cognitive decline.
Progressive frontal alopecia.
Pathology: peripherally placed sarcoplasmic masses and myofibrils. Hypertrophy of type 1 fibers with centrally placed nucleus.
DM2 – , later onset, AD, proximal muscle weakness, myotonia, cataracts. CCTG repeat
באיזה מהמצבים הבאים לא מופיע כאב שרירים לאחר מאמץ קצר:
א. חסר בפוספורילאז שרירי (McArdle)
ב. חסר בקרניטין פלמיטיל טרנספראז (CPT)
ג. היפותירואידיזם
ד. פיברומיאלגיה
ה. לאחר מחלה ממושכת
ב. CPT
McArdleDiseae – pg 1447 Myophosphorylase deficiency – conversion of glycogen to glucose-6-phosphate. Weakness, stiffness and pain on using muscles. Second wind phenomena, no raised lactic acidosis and EMG silent
CPT – pg 1449 AR recessive disease of lipid metabolism – atacks of myalgia, cramps, muscle weakness and tightness precipitated by prolonged sustained exercise
Hypothyroidism pg 1451 – diffuse myalgia
Fibromyalgia pg 1464 – focal areas of pain produced by 4kg of digital pressure
באיזה מהמצבים הבאים אין מיאלגיה?
1. steroid myopathy
2. alcoholic myopathy
3. temporal arteritis
4. hypothyroidism
5. Issac’s syndrome
- steroid myopathy
Steroid myopathy – proximal limb and girdle weakness, EMG normal or slightly myopathic, biopsy atrophic fibres no inflammatory cells. CPK normal. Also there is an acute steroid myopathy associated with critical illness – with necorsis and vacouliation of type 2 fibres. No myalgia asscoaited
Alcoholic myopathy – two types – one painless and predominantly proximal weakness after prolonged drinking and with hypokalaemia
The other – acute alcoholic myopathy – severe pain, tenderness and oedema of muscles associated with renal damage with no hypokalaemia
Temporal arthritis and PMR – associated with myalgia
Hypothyroidism associated with myalgia
Isaac’s syndrome – Continuous muscle fiber activity – Widespread myokymia with delayed muscle relaxation. Myalgia mild but present
בן 20 עם חולשת שרירים פרוקסימלים של הרגליים.
CPK 2500
איזו אבחנה אינה סבירה
א. becker muscular dystrophy
ב. hypothyroidism
ג. Inclusion body myositis
ד. polymyositis
ה. חסר ראשוני של קרניטין
ג. IBM
Table 45-6
FEATURES OF TOXININDUCED
MYOPATHIES (11)
Necrotising myopathy (rhabdomyolysis) (10)
Steroid myopathy (3)
Hypokalemic myopathy (5)
Amphiphillic cationic drug myopathy (lysosomal storage, lipidosis) (3)
Impaired protein synthesis (1)
Antimicrotubular myopathy (2)
Inflammatory (myopathy) (3)
Fasciitis, perimyositis, microangiopathy (2)
Mitochondrial myopathy (2)
Various (4)
Local myopathy due to IM injection (2)
איזו מהתשובות הבאות לגבי
critical illness myopathy (acute steroid myopathy)
אינה נכונה
א. elevated CPK
ב. EMG shows spontanious activity
ג. איבוד פילמנטים של מיוזין הינו ממצא אופייני
ד. רוב החולים נותרים עם נכות קבועה וקשה
ה. החולשה מופיעה לאחר שיפור במחלה הסיסטמית
ד. רוב החולים נותרים עם נכות קבועה וקשה- לא נכון לגבי מיופתיה של מחלה סופנית!.
The severe generalized muscle weakness usually becomes evident when the systemic illness subsides
serum CK is elevated, at least early in the process.The EMG discloses the characteristic features of a myopa thy; often there are fibrillations as well, theorized to be a result of separation of the motor endplate region from intact segments of muscle fibers. A concurrent polyneuropathy and any residual effects of neuromuscular blockade can be excluded by appropriate electrophysiologic studies. Muscle biopsy shows varying degrees of necrosis dvacuolation a ecg ma y type 2 fibers. The iden tifyinghistologic feature is a striking loss of thick (myo sin) laments. Severe degrees of muscle necrosis occur d have been accomped by massively elevated CK levels and by myoglobinuria with renal faure
Most of our patients with acute myopathy have recovered over a period of 6 to 12 weeks after the corticosteroid agent has been greatly reduced in dose or withdrawn, but a few have remained weak for as long as a year.
Figure 45-1. Schematic of the major subcellular
components of a myofibril. The transverse
(T) system, which is an invagination
of the plasma membrane of the cell, surrounds
the myofibril midway between the
Z lines and the center of the A bands; the T
system is approximated to, but apparently
not continuous with, dilated elements (terminal
cisternae) of the sarcoplasmic reticulum
on either side. Thus, each sarcomere
(the repeating Z-line-to-Z-line unit) contains
two “triads,” each composed of a pair of terminal
cisternae on each side of the T tubule.
(From Peter, by permission.)
Table 45-1
DUCHENNE/BECKER, EMERY-DREIFUSS, LIMB-GIRDLE, AND RELATED MAJOR MUSCULAR DYSTROPHIES
The molecular organization of the dystrophin-glycoprotein complex in the membrane and sarcolemma and endoplasmic reticulum-Golgi apparatus. These proteins are related to Duchenne, limb-girdle, Miyoshi, and certain congenital dystrophies
Expanded schematic of the nuclear and contractile proteins of the muscle. These proteins are referable to Emery-Dreifuss dystrophy and a number of the distal and the congenital dystrophies, as well as several of the limb-girdle dystrophies. Details in text.
Table 45-2
SELECTED MUSCULAR DYSTROPHIESa
Table 45-3
DISTAL MUSCULAR DYSTROPHIES
Table 45-4
CONGENITAL MUSCULAR DYSTROPHIES (CMD)
Table 45-5
THE GLYCOGENOSES AFFECTING SKELETAL MUSCLEa
Table 45-6
FEATURES OF TOXIN-INDUCED MYOPATHIES
Table 45-7
THE MAIN CAUSES OF ARTHROGRYPOSIS
Table 45-8
THE MAIN CONGENITAL MYOPATHIES
בדיקת EMG - מחט במצב של קונטרקטורה פיזיולוגית אמיתית
) true physiologic contracture (
תדגים בסבירות גבוהה:
א. התפרקויות מהירות גבוהות מתח
ב. התפרקויות מיוטוניות
ג. פעילות ספונטניות של סיבי שריר
ד. שקט חשמלי
שקט חשמלי
מה הכי סביר שיגרום לחולשת שרירים כואבת ?
1. Polymyositis
2. IBM
3. דיסטרופיה
4. Drug induced myopathy
Drug induced myopathy
מטופל לוקח
atorvastatin,
מפתחמיופתיהכואבתנקרוטית.
1. ANTI SRP
2. ANTICN1-NT5CIA
3. ANTI JO
4. HMG REDUCTASE
HMG רדוקטז = הרעלת סטטינים
In addition to the direct toxicity, there is an autoantibody syndrome directed against HMGCo-A reductase, which may be induced by statins (of any type) or occur spontaneously and may cause necrotizing myopathy.
קצת על המסיחים האחרים
א. necrotizing inflammatory myositis
ב. IBM
ג. PM/DM
A proportion of cases of severe, necrotizing inflammatory myositis show specific antibodies that are directed against a cytoplasmic ribonucleoprotein complex (SRP), or against a protein complex that is a nuclear helicase (Mi-2). These are now classified as separate entities from DM and in some series have carried a heightened risk of cardiac muscle inflammatory involvement. Similarly, in the category of necrotizing inflammatory myositis, a proportion of patients display antibodies to HMGCR, the target of statin drugs, but may also be present without exposure to these drugs. Although these various autoantibodies, with the possible exception of anti-Jo1, have not been especially useful as primary diagnostic tools, they do have a role in refining diagnosis.
תיאור של מטופל בן 60 עם גורמי סיכון ווסקולרים, מתקבל בשל הפרעת תחושה בכפות הרגליים וכפות הידיים, ירידה בהחזר אכילס, בנוסף כאבי שרירים קלים
cpk 550,
איזה תרופה אין צורך להפסיק לו?
1. קולכיצין
2. לבטולול
3. אמיודרון
4. כלורוקווין
לבטולול לא עושה מיופתיה
Colchicine-
* myopathic syndrome: antimicrotubular myopathy, (has also produced an acute necrotizing myopathy)
* clinical features: myoneuropathy-Proximal weakness +/- neuropathy- reflexes are diminished and there is mild distal sensory loss.
* other possible neurologic syndromes: rarely- colchicine-induced hypokalemic periodic paralysis and also of myotonia.
* pathology: Vacuolar myopathy
* laboratory findings: CPK mild elevation.
Amiodarone-
* myopathic syndrome: amphiphilic cationic drug myopathy (lysosomal storage, “lipidosis”)
* clinical features: cardiomyopathy
* pathology: ??
* laboratory findings: ??
* other possible neurologic syndromes: PTC (as an infrequent idiosyncratic effect), symmetrical subacute sensorimotor paralysis (polyneuropathy).
Chloroquine
* myopathic syndrome: amphiphilic cationic drug myopathy (lysosomal storage, “lipidosis”)
* clinical features: Proximal muscle pain and weakness, sensory motor neuropathy
* pathology: Vacuole formation, optically dense structures
* laboratory findings: CPK mild elevation.
* other possible neurologic syndromes: unilateral/bilateral optic neuropathy
תיאור של חולשת שרירים
EMG- תבנית של אמפליטודה נמוכה וגיוס מוקדם
בביופסיה הסננת לימפוציטים. איזו מחלה לא מתאימה?
1. Inclusion Body Myopathy
2. מיוטוניק דיסטרופי
3. דרמטומיוזיטיס
myotonic dystrophy
תשובה 4 אינה נכונה.
The energy for muscle contraction is provided by hydrolysis (ATP) to (ADP); ATP is restored by phosphocreatine and ADP acting in combination. These reactions are particularly important during brief, high-intensity exercise. During periods of prolonged muscle activity, rephosphorylation requires the availability of carbohydrates, fatty acids, and ketones, which are catabolized in mitochondria. Glycogen followed by blood glucose and The fatty acids in the blood, derived mainly from adipose tissue and intracellular lipid stores, constitute the major sources of energy. Carbohydrate is metabolized during aerobic and anaerobic phases of metabolism; the fatty acids are metabolized only aerobically.
Resting muscle derives approximately 70 percent of its energy from the oxidation of long-chain fatty acids. During a short period of intense exercise, the muscle uses carbohydrate derived from glycogen stores; myophosphorylase is the enzyme that initiates the metabolism of glycogen. With longer aerobic exercise, blood flow to muscle and the availability of glucose and fatty acids are increased. with exhaustion of glycogen stores, energy is provided by oxidation of fatty acids. Thus, muscle failure at a certain phase of exercise is predictive of the type of energy failure. A rising blood concentration of β-hydroxybutyrate reflects the increasing oxidation of fatty acids, and an increase in blood lactate reflects the anaerobic metabolism of glucose. The cytochrome oxidative mechanisms are essential in both aerobic and anaerobic muscle metabolism;
It follows from these observations that the efficiency and endurance of muscular contraction depend on a constant supply of glycogen, glucose, and fatty acids,
and on the adequacy of the enzymes committed to their metabolism
מה ההבדל בין שרירים גדולים לשרירי עיניים ?
- יחס נמוך שלנוירונים מוטוריםלסיבי שריר
- בסיבים גדולים יש ריבויגליקוזימונאגליקנים
- בסיבים גדולים ריבוימיטוכנדריות
- בסיבים גדוליםדיסטרופין
בסיבים גדולים יש דיסטרופין (בשרירי עיניים אין דיסטרופין ובגלל זה הם לא מעורבים במחלת דושן ובקר)
אישה צעירה שמתכננת להרות, יש לה
CPK
מגובר במאות בודדות וכן עדות לסובכים גדולים. איזו צביעה נחפש בביופסייה?
1. דיסטרופין
2. דיספרלין
3. קונגו רד
דיסטרופין
האישה בשאלה היא
asymptomatic carrier
של דושן
תיאורשלדושן.מהעודמאפייןאתהמחלה?
1. קונטרקטורות
2. קרדיומויופתיה
3. דמנציה
קונטרוקטורות
בדושן אין קרדיומיופתיה אלא אריטמיות משניות לפיברוזיס לבבי. ויש להם עיכוב התפתחותי עם איי קיו נמוך אבל אין מהלך פרוגרסיבי של ירידה קוגניטיבית.
בן 18 מתאמן לקראת גיוסו לצבא. מתלונן על חולשת שרירים במאמץ. במבחן איסכמיה אמוניה גבוהה ללא לקטט. מה האנזים הפגוע?
1. Acid maltase
2. myophosphorylase
3. Carnitine palmoitoyle transferase
4. centronuclear myopathy
myophosphorylase
McArdle Disease
Glyogenosis
-muscle cramps after exercise.
Initial complaints in any age of weakness, stiffness and
pain on using limbs
Exercise causes contractures
May be associated with myoglobinuria
Second wind phenomena
* McArdle – Myophosphorylase (glycogen to G-6-P)
* Tarui – Phosphofructokinase (G-6-P to glucose)
Muscles in contraction – electrically silent
Muscle does not produce lactic acid
Diagnosis – muscle biopsy
Rx: sucrose, reduced physical activity
קצת על המסיחים האחרים-
1. Acid Maltase – POMPE
Deficiency of acid maltase and alpha glucosidase GAA gene
- If in infancy – skeletal muscles weak, enlarged heart and liver
Rapidly progressive and fatal.
EMG – myopathic, fibrillations, pseudomyotonia
Large amount of glycogen accumulates in muscle, heart, liver, SC and brain. - Childhood form – slower progression of all skeletal msucles. No cardiomegaly or
Hepatomegaly. - Adult form – more benign truncal and proximal limb myopathy. Adult may present with breathing difficulties.
EMG – brief motor unit potentials, fibrillations, positive waves, bizarre discharges
Raised CK
IX – test for alpha glucosidase
Rx – enzyme replacement therapy available – recombinant Alpha-Glucosidase
-
Carnitine Palmitoyltransferase:
AR
CPT gene
Males predominantly
2nd decade
Attacks of myalgia, cramps, weakness , tightness, stiffness.
Precipitated by exercise and fasting
Myoglobinuria
No second wind
Persistence of weakness after attack uncommon
CK high high
Between attacks muscles normal
Ix: CPT test
Rx: high carb low fat
bezafibrate
- Congenital structural myopathies
No loss of muscle But morphological abnormality
Lack of muscle bulk, hypotonia, Weakness of limbs, dysmorphic features
Early onset and lack of progression
No treatment
-
Central core myopathy:
Appears in childhood
AD
Spares facial, bulbar, occular muscles
EMG – brief small amplitude MUPs
CK normal
Risk of malignant hyperthermia
Pathology – presence in central portion of muscle a dense amorphous condensation of myofibrils
* Nemaline rod body
Hypotnoia also involves face, lingual and pharyngeal.
Narrow face, open mouth, arched palate.
In adult form – involvement of respiratory muscles
Associated with monoclonal gammopathy
Pathology – rods and coils
-
Centronuclear – myotubular myopathy:
All muscles involved but:
Distinctive features – ptosis, occular palsy, Weakness of facial and cervical muscles.
Pathology – small muscles, central nucleation
- Ryanodine receptor associated with Neuroleptic malignant syndrome
Malignant hyperthermia, and congenital myopathies – central core and nemaline rod*
מטופל עם אירועים של חולשת שרירים ונוקשות לאחר מאמץ. ובבדיקת מחט שקט חשמלי בשריר מכווץ.
1. אסיד מלטאז
2. מיופוספורילאז
3. דיספרלין
4. דיסטרופין
מיופוספורילז
McArdle Disease
Glyogenosis
-muscle cramps after exercise.
Initial complaints in any age of weakness, stiffness and
pain on using limbs
Exercise causes contractures
May be associated with myoglobinuria
Second wind phenomena
* McArdle – Myophosphorylase (glycogen to G-6-P)
* Tarui – Phosphofructokinase (G-6-P to glucose)
Muscles in contraction – electrically silent
Muscle does not produce lactic acid
Diagnosis – muscle biopsy
Rx: sucrose, reduced physical activity
Acid Maltase – POMPE
Deficiency of acid maltase and alpha glucosidase GAA gene
- If in infancy – skeletal muscles weak, enlarged heart and liver
Rapidly progressive and fatal.
EMG – myopathic, fibrillations, pseudomyotonia
Large amount of glycogen accumulates in muscle, heart, liver, SC and brain. - Childhood form – slower progression of all skeletal msucles. No cardiomegaly or
Hepatomegaly. - Adult form – more benign truncal and proximal limb myopathy. Adult may present with breathing difficulties.
EMG – brief motor unit potentials, fibrillations, positive waves, bizarre discharges
Raised CK
IX – test for alpha glucosidase
Rx – enzyme replacement therapy available – recombinant Alpha-Glucosidase
מטופל צעיר בעת מאמץ גופני אינטנסיבי מפתח התכווצויות שרירים, כאב, שתן בצבע קולה. לאחר מנוחה יש שיפור. בעת בדיקת
EMG – שקט בשריר.
מה האנזים?
1. Myophosphorylase
2. CPT
3. Acid maltase
4. ATPase
מיופוספורילז
McArdle Disease
Glyogenosis
-muscle cramps after exercise.
Initial complaints in any age of weakness, stiffness and
pain on using limbs
Exercise causes contractures
May be associated with myoglobinuria
Second wind phenomena
* McArdle – Myophosphorylase (glycogen to G-6-P)
* Tarui – Phosphofructokinase (G-6-P to glucose)
Muscles in contraction – electrically silent
Muscle does not produce lactic acid
Diagnosis – muscle biopsy
Rx: sucrose, reduced physical activity
קצת על המסיחים האחרים-
1. Acid Maltase – POMPE
Deficiency of acid maltase and alpha glucosidase GAA gene
- If in infancy – skeletal muscles weak, enlarged heart and liver
Rapidly progressive and fatal.
EMG – myopathic, fibrillations, pseudomyotonia
Large amount of glycogen accumulates in muscle, heart, liver, SC and brain. - Childhood form – slower progression of all skeletal msucles. No cardiomegaly or
Hepatomegaly. - Adult form – more benign truncal and proximal limb myopathy. Adult may present with breathing difficulties.
EMG – brief motor unit potentials, fibrillations, positive waves, bizarre discharges
Raised CK
IX – test for alpha glucosidase
Rx – enzyme replacement therapy available – recombinant Alpha-Glucosidase
-
Carnitine Palmitoyltransferase:
AR
CPT gene
Males predominantly
2nd decade
Attacks of myalgia, cramps, weakness , tightness, stiffness.
Precipitated by exercise, febrile illness and fasting
Myoglobinuria
No second wind
Persistence of weakness after attack uncommon
CK high high
Between attacks muscles normal
Ix: CPT test
Rx: high carb low fat
bezafibrate
חייל בן 18 בטירונות, תוך כדי דלקת ריאות קשה מלווה בחום גבוה מתלונן על כאבי שרירים ומדווח על הופעת שתן בצבע חום.
CPK- 680,000
מהו האנזים הפגוע?
1. Carnitine palmityl transferase
2. myophosphorylase
3. phosphofructokinase
4. acid maltse
5. myoadenylate deaminase
Carnitine palmityl transferase
Carnitine Palmitoyltransferase:
AR
CPT gene
Males predominantly
2nd decade
Attacks of myalgia, cramps, weakness , tightness, stiffness.
Precipitated by exercise, febrile illness and fasting
Myoglobinuria
No second wind
Persistence of weakness after attack uncommon
CK high high
Between attacks muscles normal
Ix: CPT test
Rx: high carb low fat
bezafibrate
חייל שצם ביום כיפור ולמחרת ביצע מסע מפרך, לאחר כיממה חולשת שרירים, שתן בצבע קולה. מה המחלה?
1. CPT
2. mcardle
3. Tauri
4. Duchenne
Carnitine palmityl transferase
Carnitine Palmitoyltransferase:
AR
CPT gene
Males predominantly
2nd decade
Attacks of myalgia, cramps, weakness , tightness, stiffness.
Precipitated by exercise, febrile illness and fasting
Myoglobinuria
No second wind
Persistence of weakness after attack uncommon
CK high high
Between attacks muscles normal
Ix: CPT test
Rx: high carb low fat
bezafibrate
מטופל לאחר מאמץ ממושך , יש כאבי שרירים ושתן כהה. אין הטבה לאחר מנוחה קלה, להפרעה במטבוליזם של איזה חומר הדבר מכוון.
1. FATTY ACID
2. AMINO ACID
3. GLYOGEN
4. גלוקוז
Fatty acid
Carnitine Palmitoyltransferase:
AR
CPT gene
Males predominantly
2nd decade
Attacks of myalgia, cramps, weakness , tightness, stiffness.
Precipitated by exercise, febrile illness and fasting
Myoglobinuria
No second wind
Persistence of weakness after attack uncommon
CK high high
Between attacks muscles normal
Ix: CPT test
Rx: high carb low fat
bezafibrate
מה נכון לגבי ההבדל בין סיבי שריר 1 ו-2
1. type 1 muscle fibers have less mitochondria
2. Type 2 muscle fibers have more myoglobin
3. type 2 muscle fibers have more myosin-ATPase
4. type 1 fibers have a faster mechanism of action
type 2 muscle fibers have more myosin-ATPase
- TYPE 1- slow twitch- Muscle cells rich in oxidative enzymes (type 1 fibers) contain more mitochondria and larger amounts of myoglobin (therefore appearing red), have slower rates of contraction and relaxation, fire more tonically, and are less fatigable than muscle fibers poor in oxidative enzymes.
- TYPE 2- fast twitch- fire in bursts and are used in quick phasic, rather than sustained, reactions.
- The amount of myosin ATPase activity, which governs the speed of contraction, is low in oxidative-rich fibers and high in glycolytic-rich fibers.
In other words- Type 1 fibers have a low content of myosin ATPase, and
Type 2 (phosphorylative-rich) fibers have a high content of this enzyme; hence type 1 fibers stain lightly and type 2 darkly at PH9
מחלת
Emery-Dreifuss muscular dystrophy
מאופיינת ב:
1. חולשת שרירים דיסטלית
2. חוסר יכולת לכופף מרפקים
3. צורך בקוצב בשל הפרעות הולכה בלב
4. לרוב הינה רציסיבית
5. אף אחד מהנ”ל
צורך בקוצב בשל הפרעות הולכה בלב
הקטע עם המרפקים- חוסר יכולת ליישר לא לכופף
Iבן 24, מאושפז עקב הפרעות קצב לב. אקו לב – הגדלה של חדר שמאל ומקטע פליטה ירוד מאוד. אחיו של המטופל מת מוות פתאומי בגיל 18. והשני סובל ממחלת שרירים מזה שנתיים. שני אחים נוספים בריאים, ושלוש האחיות בריאות. בבדיקתו: חולשה פרוקסימלית סימטרית קלה בחגורת הכתפיים, הגבלה בכיפוף במרפק וחולשת אקסטנסורים של הצוואר. פונדוס תקין. איזה מחלה:
- Limb girdle
- Emery Dreifuss
- Nemaline
- Myotonic dystrophy
- Tangier
EMERY DREiFUSS
This is a highly diverse group of disorders that encompasses at least six different genetic types, the most common probably being an X-linked muscular dystrophy characterized by the special feature of muscle contractures.
That process is relatively benign in comparison with the Duchenne dystrophy.
The primary gene defect is a deficiency of the protein emerin, a constituent of the nuclear membrane, encoded by a gene on the X chromosome . Though may be AR . The age of onset varies from childhood to late adolescence or adulthood. Weakness affects first the upper arm and pectoral girdle musculature and later the pelvic girdle and the distal muscles in the lower extremities.
The distinguishing feature of the disease is the early appearance of contractures in the flexors of the elbow, extensors of the neck, and posterior calf muscles. Facial muscles are affected occasionally. There is no hypertrophy or pseudohypertrophy, and mentation is unaffected. However, severe cardiomyopathy with variable sinoatrial
and atrioventricular conduction defects is a common accompaniment.
The course of the myopathy is generally benign, more like that of Becker dystrophy, but weakness and contractures are severe in some cases and sudden cardiac death is a not infrequent occurrence. For this reason, close monitoring by a cardiologist and the prophylactic insertion of a pacemaker at the appropriate time may be lifesaving.
The less common types of Emery-Dreifuss dystrophy, as mentioned, may have a scapuloperoneal (FHL-1 gene) or humeroperoneal (laminin mutation).
בחור עם חולשת שרירים, קונטרקטורות
AV BLOCK
ללא פגיעה קוגניטיבית. מה האבחנה?
1. Emery Dreifuss
2. Becker Dystrophy
3. Duchenne muscular dystrophy
4. Facioscapulohumeral muscular dystrophy
EMERY DREiFUSS
This is a highly diverse group of disorders that encompasses at least six different genetic types, the most common probably being an X-linked muscular dystrophy characterized by the special feature of muscle contractures.
That process is relatively benign in comparison with the Duchenne dystrophy.
The primary gene defect is a deficiency of the protein emerin, a constituent of the nuclear membrane, encoded by a gene on the X chromosome . Though may be AR . The age of onset varies from childhood to late adolescence or adulthood. Weakness affects first the upper arm and pectoral girdle musculature and later the pelvic girdle and the distal muscles in the lower extremities.
The distinguishing feature of the disease is the early appearance of contractures in the flexors of the elbow, extensors of the neck, and posterior calf muscles. Facial muscles are affected occasionally. There is no hypertrophy or pseudohypertrophy, and mentation is unaffected. However, severe cardiomyopathy with variable sinoatrial
and atrioventricular conduction defects is a common accompaniment.
The course of the myopathy is generally benign, more like that of Becker dystrophy, but weakness and contractures are severe in some cases and sudden cardiac death is a not infrequent occurrence. For this reason, close monitoring by a cardiologist and the prophylactic insertion of a pacemaker at the appropriate time may be lifesaving.
The less common types of Emery-Dreifuss dystrophy, as mentioned, may have a scapuloperoneal (FHL-1 gene) or humeroperoneal (laminin mutation).
איזו מחלה מתאפיינת בהופעה של קונטרקטורות:?
א. Duchenne muscular dystrophy
ב. Myotonic dystrophy
ג. Becker muscular dystrophy
ד. Emery-Dreifuss muscular Dystrophy
אוקי אז זה נכון שיש גם בדושן..
אבל באמרי דרייפוס יש הכי הרבה
בת 45 עם לופוס + תסמונת שיוגרן מלוננת על חודש עם קשיי נשימה, חולשת שרירים פרוגרסיבית וחיוורון.כחלון לסירוגין באצבעות הידיים.
CPK סביב 2000
מה האבחנה הסבירה?
1. dermatomyositis
2. synthetase syndrome
3. IBM
4. vasculitis
5. rhabdomyoltis
Synthetase syndrome
Of greater interest are the findings that 20 to 30 percent of patients with DM have antibodies against various cellular components of muscle, in particular, antibodies directed against cytoplasmic transfer ribonucleic acid (tRNA) synthetases (antiJo1), or against the tRNA itself. These are found when the myositis is
coupled with an expanded illness that involves other tissues. The clinical disorders associated with these antibodies usually combine myositis with (1) interstitial lung disease but also (2) arthritis, (3) Raynaud syndrome, and (4) thickening of the skin of the hands (“mechanic’s hands”). Following from the designation of the main type of antibody, these have been termed synthetase syndromes.
synthetase syndromes: autoimmune myopathy + connective tissue disease
( SLE, RA, Sjorgen’s syndrome, systemnic sclerosis)
Extra-muscular manifestations
* interstitial lung disease
* arthritis
* raynaud syndrome
* fever
* mechanich’s hands
* Dermatomyositis rash (!)
Symmetric weakness (can be very mild)
מוצא פרסי אינו תומך באבחנה- הולך יותר עם nonaka (GME/hereditary IBM)
Perifasicullar atrophy= dermatomyositis
MELAS
מה אינו אופייני ל-
adult onset POMPE disease
1. קוצר נשימה במאמצים
2. אורטופניאה
3. צבירת פחמן דו חמצני
4. forced vital capacity (FVC) ירוד
5. אלקטרומיוגרפיה של שרירים פאראספינליים- תקין EMG
בפומפה-
. אלקטרומיוגרפיה של שרירים פאראספינליים- אינו תקין EMG
נראה גם פיברילציות ב
EMG
וכן נראה CPK
תקין או מעט מוגבר
In the third, or adult, form there is a more benign truncal and proximal limb myopathy that is slowly progressive over many years and death is usually the result of weakness of respiratory muscles. At times, the only severe weakness is of the diaphragm,
The liver and heart are not enlarged. CK values can be normal or slightly increased. The EMG discloses a number of abnormalities—brief motor unit potentials, fibrillation potentials, positive waves, bizarre high-frequency discharges, and occasional myotonic discharges (without clinical evidence of myotonia).
Acid Maltase – POMPE
Deficiency of acid maltase and alpha glucosidase GAA gene
- If in infancy – skeletal muscles weak, enlarged heart and liver Rapidly progressive and fatal.
EMG – myopathic, fibrillations, pseudomyotonia
Large amount of glycogen accumulates in muscle, heart, liver, SC and brain. - Childhood form – slower progression of all skeletal muscles. No cardiomegaly or Hepatomegaly.
-
Adult form – more benign truncal and proximal limb myopathy. Adult may present with breathing difficulties.
EMG – brief motor unit potentials, fibrillations, positive waves, bizarre discharges
IX – test for alpha glucosidase
Rx – enzyme replacement therapy available – recombinant Alpha-Glucosidase
מחלת
OPMD- Oropharyngeal muscular dystrophy
מאופיינת ב:
1. פטוזיס+ אופטלמופלגיה קשה+ קושי בבליעה
2. פטוזיס + קושי בבליעה+ חולשת שרירי פנים
3. פטוזיס + קושי בבליעה+ חולשת שרירי גפיים
4. פטוזיס + אופטלמופלגיה קשה + פולינוירופתיה
פטוזיס+ קושי בבליעה+ חולשת שרירי גפיים
Oculopharyngeal dystrophy is inherited as an autosomal dominant trait and is unique in its late onset (usually after the forty-fifth year) and the restricted muscular weakness, manifest mainly as a bilateral ptosis and dysphagia.
early French-Canadian immigrant, who was the progenitor of 249 descendants with the disease. Other families showing a dominant (rarely recessive) pattern of inheritance and a number of sporadic cases have been observed in many parts of the world.
Difficulty in swallowing and change in voice are associated with slowly progressive ptosis. Swallowing becomes so difficult that food intake is limited, resulting in cachexia, which can be ameliorated by cutting the cricopharyngeus muscles, or, if that fails, by a gastrostomy or nasogastric tube. Later in the disease, in some families the external ocular muscles and shoulder and pelvic muscles become weakened and atrophic to a varying extent. In the few autopsied cases, a loss of fibers of modest proportions was widespread in these and many other muscles. Rimmed vacuoles in the sarcoplasm and, by electron microscopy, intranuclear tubular filaments are characteristic but not specific histologic findings (these features are seen in other myopathies, particularly in inclusion body myositis). The brainstem nuclei and cranial nerves are normal. As in the other mild and restricted muscular dystrophies, the serum CK and aldolase levels are normal and the EMG is altered only in the affected muscles.
The gene product of the mutatued gene, PABN1, is a protein that binds to RNA (poly-A binding protein). The defect is an expansion of a string of alanines. Normally, there are 6 repeats; in dominantly inherited oculopharyngeal dystrophy, there are 8 to 13 repeats; in the recessively inherited form there are 7 repeats on each allele. Thus this represents one of the most subtle nucleotide expansion diseases yet discovered
מה היא הסיבה השכיחה ביותר למוות מוקדם במטופלים הסובלים מ-
oculopharyngeal muscular dystrophy
1. הפרעה בקצב הלב
2. סיבוכי דיספגיה
3. דמנציה
4. אי ספיקת כליות
5. חולשת שרירי הנשימה
סיבוכי דיספגיה
Oculopharyngeal dystrophy is inherited as an autosomal dominant trait and is unique in its late onset (usually after the forty-fifth year) and the restricted muscular weakness, manifest mainly as a bilateral ptosis and dysphagia.
early French-Canadian immigrant, who was the progenitor of 249 descendants with the disease. Other families showing a dominant (rarely recessive) pattern of inheritance and a number of sporadic cases have been observed in many parts of the world.
Difficulty in swallowing and change in voice are associated with slowly progressive ptosis. Swallowing becomes so difficult that food intake is limited, resulting in cachexia, which can be ameliorated by cutting the cricopharyngeus muscles, or, if that fails, by a gastrostomy or nasogastric tube. Later in the disease, in some families the external ocular muscles and shoulder and pelvic muscles become weakened and atrophic to a varying extent. In the few autopsied cases, a loss of fibers of modest proportions was widespread in these and many other muscles. Rimmed vacuoles in the sarcoplasm and, by electron microscopy, intranuclear tubular filaments are characteristic but not specific histologic findings (these features are seen in other myopathies, particularly in inclusion body myositis). The brainstem nuclei and cranial nerves are normal. As in the other mild and restricted muscular dystrophies, the serum CK and aldolase levels are normal and the EMG is altered only in the affected muscles.
The gene product of the mutatued gene, PABN1, is a protein that binds to RNA (poly-A binding protein). The defect is an expansion of a string of alanines. Normally, there are 6 repeats; in dominantly inherited oculopharyngeal dystrophy, there are 8 to 13 repeats; in the recessively inherited form there are 7 repeats on each allele. Thus this represents one of the most subtle nucleotide expansion diseases yet discovered
מה הסיבוך השכיח של
oculopharyngeal dystrophy
1. רטיניטיס
2. דיספאגיה
3. הפרעות קצב
דיספאגיה
Oculopharyngeal dystrophy is inherited as an autosomal dominant trait and is unique in its late onset (usually after the forty-fifth year) and the restricted muscular weakness, manifest mainly as a bilateral ptosis and dysphagia.
early French-Canadian immigrant, who was the progenitor of 249 descendants with the disease. Other families showing a dominant (rarely recessive) pattern of inheritance and a number of sporadic cases have been observed in many parts of the world.
Difficulty in swallowing and change in voice are associated with slowly progressive ptosis. Swallowing becomes so difficult that food intake is limited, resulting in cachexia, which can be ameliorated by cutting the cricopharyngeus muscles, or, if that fails, by a gastrostomy or nasogastric tube. Later in the disease, in some families the external ocular muscles and shoulder and pelvic muscles become weakened and atrophic to a varying extent. In the few autopsied cases, a loss of fibers of modest proportions was widespread in these and many other muscles. Rimmed vacuoles in the sarcoplasm and, by electron microscopy, intranuclear tubular filaments are characteristic but not specific histologic findings (these features are seen in other myopathies, particularly in inclusion body myositis). The brainstem nuclei and cranial nerves are normal. As in the other mild and restricted muscular dystrophies, the serum CK and aldolase levels are normal and the EMG is altered only in the affected muscles.
The gene product of the mutatued gene, PABN1, is a protein that binds to RNA (poly-A binding protein). The defect is an expansion of a string of alanines. Normally, there are 6 repeats; in dominantly inherited oculopharyngeal dystrophy, there are 8 to 13 repeats; in the recessively inherited form there are 7 repeats on each allele. Thus this represents one of the most subtle nucleotide expansion diseases yet discovered
בן 60 יליד קנדה מאושפז במחלקה פנימית בשל
aspiration pneumonia
נקראת לייעוץ בשל צניחת עפעפיים ובבדיקתך אכן צניחת עפעפיים עד לאמצע האישון לערך, ללא הפרעה בתנועות גלגלי העיניים. התופעה קיימת מזה 5 שנים וגוברת בהדרגה, לאח יש תופעה דומה. איזה ממצא מבין הבאים צפוי שתמצא בחולה הנ”ל?
1. anti achetylcholine receptor Ab
2. Anti voltage gated calcium channel antibodies
3. Elevated T3-T4
4. GCG repeat expansion in Poly- A binding protein gene
5. Deletion mutation in the mitochondrial DNA
GCG repeat expansion in Poly- A binding protein gene
Oculopharyngeal dystrophy is inherited as an autosomal dominant trait and is unique in its late onset (usually after the forty-fifth year) and the restricted muscular weakness, manifest mainly as a bilateral ptosis and dysphagia.
early French-Canadian immigrant, who was the progenitor of 249 descendants with the disease. Other families showing a dominant (rarely recessive) pattern of inheritance and a number of sporadic cases have been observed in many parts of the world.
Difficulty in swallowing and change in voice are associated with slowly progressive ptosis. Swallowing becomes so difficult that food intake is limited, resulting in cachexia, which can be ameliorated by cutting the cricopharyngeus muscles, or, if that fails, by a gastrostomy or nasogastric tube. Later in the disease, in some families the external ocular muscles and shoulder and pelvic muscles become weakened and atrophic to a varying extent. In the few autopsied cases, a loss of fibers of modest proportions was widespread in these and many other muscles. Rimmed vacuoles in the sarcoplasm and, by electron microscopy, intranuclear tubular filaments are characteristic but not specific histologic findings (these features are seen in other myopathies, particularly in inclusion body myositis). The brainstem nuclei and cranial nerves are normal. As in the other mild and restricted muscular dystrophies, the serum CK and aldolase levels are normal and the EMG is altered only in the affected muscles.
The gene product of the mutatued gene, PABN1, is a protein that binds to RNA (poly-A binding protein). The defect is an expansion of a string of alanines. Normally, there are 6 repeats; in dominantly inherited oculopharyngeal dystrophy, there are 8 to 13 repeats; in the recessively inherited form there are 7 repeats on each allele. Thus this represents one of the most subtle nucleotide expansion diseases yet discovered
באיזו ממחלות השרירים הבאות אין פגיעה בלב?
1. myotonic dystrophy
2. friedreich’s ataxia
3. oculopharyngeal muscular dystrophy
4. Emery Dreifuss muscular dystrophy
5. Becker type muscular dystrophy
Oculopharyngeal dystrophy is inherited as an autosomal dominant trait and is unique in its late onset (usually after the forty-fifth year) and the restricted muscular weakness, manifest mainly as a bilateral ptosis and dysphagia.
early French-Canadian immigrant, who was the progenitor of 249 descendants with the disease. Other families showing a dominant (rarely recessive) pattern of inheritance and a number of sporadic cases have been observed in many parts of the world.
Difficulty in swallowing and change in voice are associated with slowly progressive ptosis. Swallowing becomes so difficult that food intake is limited, resulting in cachexia, which can be ameliorated by cutting the cricopharyngeus muscles, or, if that fails, by a gastrostomy or nasogastric tube. Later in the disease, in some families the external ocular muscles and shoulder and pelvic muscles become weakened and atrophic to a varying extent. In the few autopsied cases, a loss of fibers of modest proportions was widespread in these and many other muscles. Rimmed vacuoles in the sarcoplasm and, by electron microscopy, intranuclear tubular filaments are characteristic but not specific histologic findings (these features are seen in other myopathies, particularly in inclusion body myositis). The brainstem nuclei and cranial nerves are normal. As in the other mild and restricted muscular dystrophies, the serum CK and aldolase levels are normal and the EMG is altered only in the affected muscles.
The gene product of the mutatued gene, PABN1, is a protein that binds to RNA (poly-A binding protein). The defect is an expansion of a string of alanines. Normally, there are 6 repeats; in dominantly inherited oculopharyngeal dystrophy, there are 8 to 13 repeats; in the recessively inherited form there are 7 repeats on each allele. Thus this represents one of the most subtle nucleotide expansion diseases yet discovered
בן 50, בוכרי עם חולשת עיניים, בליעהודיספוניה. מה עוד עשוי להיות בהמשך ?
1. CKמוגבר פי 10-100
2. חולשת חגורת כתפיים
3. מיוטוניהבכפות הידיים
4. נוירופתיהדיסטליתבEMG
חולשה בחגורת הכתפיים
Oculopharyngeal dystrophy is inherited as an autosomal dominant trait and is unique in its late onset (usually after the forty-fifth year) and the restricted muscular weakness, manifest mainly as a bilateral ptosis and dysphagia.
early French-Canadian immigrant, who was the progenitor of 249 descendants with the disease. Other families showing a dominant (rarely recessive) pattern of inheritance and a number of sporadic cases have been observed in many parts of the world.
Difficulty in swallowing and change in voice are associated with slowly progressive ptosis. Swallowing becomes so difficult that food intake is limited, resulting in cachexia, which can be ameliorated by cutting the cricopharyngeus muscles, or, if that fails, by a gastrostomy or nasogastric tube. Later in the disease, in some families the external ocular muscles and shoulder and pelvic muscles become weakened and atrophic to a varying extent. In the few autopsied cases, a loss of fibers of modest proportions was widespread in these and many other muscles. Rimmed vacuoles in the sarcoplasm and, by electron microscopy, intranuclear tubular filaments are characteristic but not specific histologic findings (these features are seen in other myopathies, particularly in inclusion body myositis). The brainstem nuclei and cranial nerves are normal. As in the other mild and restricted muscular dystrophies, the serum CK and aldolase levels are normal and the EMG is altered only in the affected muscles.
The gene product of the mutatued gene, PABN1, is a protein that binds to RNA (poly-A binding protein). The defect is an expansion of a string of alanines. Normally, there are 6 repeats; in dominantly inherited oculopharyngeal dystrophy, there are 8 to 13 repeats; in the recessively inherited form there are 7 repeats on each allele. Thus this represents one of the most subtle nucleotide expansion diseases yet discovered
מטופל ואמו חולים באותה מחלה עם פטוזיס וחולשה בשרירי הגפיים וגם הגבלה ניכרת בתנועות העיניים דו”צ. ללא דיפלופיה.
- Progressive external opthalmoplegia
- OPMD (oculopharyngeal muscular dystrophy)
- Facioscapulohumeral dystrophy
- Emery Dreifuss
Progresive external ophtalmoplegia
slowly progressive myopathy, often limited to extraocular muscles, ptoss and balanced opthalmoparesis. M=F, may be AD/AR or mitochondrial (Kearne sayer. diplopia is uncommon because opthalmoparesis is balanced.
בן 30 עםפטוזיסמילדות , הפרעה בתנועות עיניים לכל הכיוונים, חולשתאורביקולריס, תגובת אישונים ואקומודציה תקינה
1. תירוקסיןנמוך
2. B12 deficiency
3. PEO
4. אוקולופרינגיאלידיסטרופי
PEO
slowly progressive myopathy, often limited to extraocular muscles, ptoss and balanced opthalmoparesis. M=F, may be AD/AR or mitochondrial (Kearne sayer. diplopia is uncommon because opthalmoparesis is balanced.
פגיעה ב
Z Bands
Myofibrillar Myopathy
Mutations of one of the proteins that relate to the
Z-disc (the connection between adjacent sarcomeres,
which are the structural units of the myofibril) of muscle
seem to be the unifying feature. Some of these abnormalities can be traced to a dominant mutation in the genes coding for the filament proteins myotilin, also implicated in one of the limb-girdle dystrophies, in desmin, and in the chaperone protein a/3-crystallin. Presumably, mutations in either gene predispose to protein aggregation, the former by destabilizing desmin and the latter by altering the capacity of the a/3-crystallin to facilitate normal desmin folding.
The diagnosis of myofibrillar myopathy is usually
made in adult life by muscle biopsy. Men and women
are equally affected. Slowly progressive weakness of the
muscles of limbs and trunk is the main clinical feature.
Both proximal and distal muscles are affected, more in
the legs than in the arms. Hyporeflexia is usual. Cardiac involvement, usually abnormalities of conduction, is present in approximately 25 percent of the patients. The pattern of inheritance is most often autosomal dominant, but autosomal recessive and X-linked patterns also have been described.
chronic thyrotoxic state
Chronic Thyrotoxic Myopathy
progressive weakness and wasting of the skeletal musculature occurring in conjunction with overt or covert (“masked”) hyperthyroidism. The thyroid disease is usually chronic and the goiter is usually of the nodular rather than the diffuse type. Exophthalmos and other classic signs of hyperthyroidism are often present but need not be. This complication of hyperthyroidism is most frequent in middle age, and men are more susceptible than women. The onset is insidious, and the weakness progresses over weeks and months. The muscular disorder as noted is most often mild in degree, but it may be so severe as to suggest progressive spinal muscular atrophy (motor system disease). Muscles of the pelvic girdle and thighs are weakened more than others (Basedow paraplegia), although all are affected to some extent, even the bulbar muscles and, albeit rarely, the ocular ones. However, the shoulder and hand muscles show the most conspicuous atrophy (not an obligatory feature). Tremor and twitching during contraction may occur, but we have not seen fasciculations. The tendon reflexes are of average briskness, possibly more lively than normal. Both the contraction and relaxation phases of the tendon reflexes are shortened, but usually this cannot be detected by the clinician.
Serum concentrations of muscle enzymes are not increased and may be reduced. The EMG is typically normal although the action potentials may be abnormally brief or polyphasic. Biopsies of muscle, except for slight atrophy of both types 1 and 2 fibers and an occasional degenerating fiber, have been normal. Muscle power and bulk are gradually restored when thyroid hormone levels are reduced to normal levels.
קצת על המסיחים האחרים:
- ALS- נראה פסיקלוציות
- SMA- Mostly inherited disease of childhood, with onset mostly in first year of life. If familial – inherited as AR chrom 5
Gene for survival of motor neuron protein with 2 alleles – the amount of SMN2 protein determines the severity and onset of disease.
Clinical: floppy, arthrogryposis, death within 1 yr.
trunk, pelvis and shoulder first affected.
Hypotonia, then all skeletal muscles, respiratory muscles affected.
Cannot sit up or hold head without support
Frog leg position
muscle enzymes normal
EMG – fibrillations, MUPs diminished or giant and polyphasic, velocities retained.
Muscle biopsy – group atrophy. Degeneration of anterior horn cells and brainstem motor nuclei.
רוב הספיינל מוסקולר אטרופי זה בילדות. סוג 4 זה אחרי גיל 30 ושם יש חולשה פרוקסימלית - lesion is in the high cervical region If the lesion is in the high cervical region, there is clumsiness in the palpation of objects and an inability to recognize the qualities of objects by touch, even though touch-pressure sensation is relatively intact. stereoanesthesia is also expressed by impaired graphesthesia and tactile localization. There may be unusual disturbances of touch and pressure, manifesting as lability of threshold, persistence of sensation after removal of the stimulus, and sometimes tactile and postural hallucination. A progressive syndrome of monoparesis, biparesis, usually of the arms, and then triparesis involving the leg on the side of the last affected arm (“around the clock“ pattern) is caused by tumors and a variety of other compressive lesions in the region of the foramen magnum and high cervical cord.
בן 56, לאחר אשפוז והנשמה על רקע ספסיס. אינו מצליח להיגמל מהנשמה. בבדיקת אלקטרומיוגרפיה יש עדות למיופתיה מה הממצא שסביר שימצא בביופסית שריר?
1. נקרוזיס סיבי טייפ 1
2. אובדן של פילמנטים עבים של מיוזין
3. אין אינקולוזיות
אובדן של פילמנטים עביר של מיוזין
Critical Illness Myopathy
In addition to the proximal myopathy induced by the long-term use of steroids, an acute and far more severe myopathy has been recognized in critically ill patients. It was described initially with cases of severe asthma in patients who were exposed to high doses of steroids for treatment. usually in the context of the administration of high doses of corticosteroids but in a few cases, with sepsis and shock without exposure to this class of medication. Moreover, the use of neuromuscular blocking agents appears to play an important complementary role in the genesis of the myopathy. Usually becomes evident when the systemic illness subsides, often as attempts are made to wean the patient from the ventilator. The tendon reflexes are normal or diminished, and there may be confounding features of a critical illness polyneuropathy. Serum CK is elevated. The **EMG **discloses the characteristic features of a myopathy; often there are fibrillations as well, theorized to be a result of separation of the motor endplate region from intact segments of muscle fibers.
Muscle biopsy shows varying degrees of necrosis and vacuolation affecting mainly type 2 fibers.
The identifying histologic feature is a striking loss of thick (myosin) filaments.
אבחנה מבדלת עיקרית-
* Critical Illness Polyneuropathy
An acute or subacute symmetrical polyneuropathy is a frequent development in critically ill and septic patients, particularly in those with failure of multiple organs. This neuropathy causes difficulty in weaning a patient from the ventilator, even as the underlying critical illness comes under control. The neuropathic process, predominantly of motor type, varies in severity from an electrophysiologic abnormality without overt clinical signs, to quadriparesis with respiratory failure. Sensory symptoms and signs are variable but tend to be mild. Usually the cranial nerves are spared and there are few or no dysautonomic manifestations.
The EMG and NCS findings of a primary axonal process with early denervation and a normal CSF distinguish this entity from the typical demyelinative form of GBS. Critical illness polyneuropathy must also be distinguished From acute critical illness myopathy that also complicates critical illness. High doses of corticosteroids, particularly in combination with neuromuscular blocking agents, have been implicated.
The acute myopathy, which affects both distal and proximal muscles, is sometimes heralded by an elevation in the serum creatine kinase (CK) concentration (at times up to several thousand units) and myopathic potentials in the EMG, and a unique degeneration of myofilaments in all the muscles is found.
שתיית אלכוהול לא קשורה למקרה זה
Critical Illness Myopathy
In addition to the proximal myopathy induced by the long-term use of steroids, an acute and far more severe myopathy has been recognized in critically ill patients. It was described initially with cases of severe asthma in patients who were exposed to high doses of steroids for treatment. usually in the context of the administration of high doses of corticosteroids but in a few cases, with sepsis and shock without exposure to this class of medication. Moreover, the use of neuromuscular blocking agents appears to play an important complementary role in the genesis of the myopathy. Usually becomes evident when the systemic illness subsides, often as attempts are made to wean the patient from the ventilator. The tendon reflexes are normal or diminished, and there may be confounding features of a critical illness polyneuropathy. Serum CK is elevated. The **EMG **discloses the characteristic features of a myopathy; often there are fibrillations as well, theorized to be a result of separation of the motor endplate region from intact segments of muscle fibers.
Muscle biopsy shows varying degrees of necrosis and vacuolation affecting mainly type 2 fibers.
The identifying histologic feature is a striking loss of thick (myosin) filaments.
אבחנה מבדלת עיקרית-
* Critical Illness Polyneuropathy
An acute or subacute symmetrical polyneuropathy is a frequent development in critically ill and septic patients, particularly in those with failure of multiple organs. This neuropathy causes difficulty in weaning a patient from the ventilator, even as the underlying critical illness comes under control. The neuropathic process, predominantly of motor type, varies in severity from an electrophysiologic abnormality without overt clinical signs, to quadriparesis with respiratory failure. Sensory symptoms and signs are variable but tend to be mild. Usually the cranial nerves are spared and there are few or no dysautonomic manifestations.
The EMG and NCS findings of a primary axonal process with early denervation and a normal CSF distinguish this entity from the typical demyelinative form of GBS. Critical illness polyneuropathy must also be distinguished From acute critical illness myopathy that also complicates critical illness. High doses of corticosteroids, particularly in combination with neuromuscular blocking agents, have been implicated.
The acute myopathy, which affects both distal and proximal muscles, is sometimes heralded by an elevation in the serum creatine kinase (CK) concentration (at times up to several thousand units) and myopathic potentials in the EMG, and a unique degeneration of myofilaments in all the muscles is found.
באיזו מחלת שרירים אין עלייה משמעותית ברמת ה-
CPK
בדם?
1. תת פעילות של בלוטת התריס
2. מיופתיה הנגרמת ע”י סטרואידים
3. פולימיוזיטיס
4. מיופתיה עקב שימוש בתכשירים להורדת רמת כולסטרול
5. דושן
מיופתיה הנגרמת ע”י סטרואידים לא תגרום לעלייה משמעותית של
CPK.
(יש לשים לב שלא מדובר בקריטיקל אילנס מיופת’י)
Steroid Induced Myopathy
2 types:
1. Chronic corticosteroid myopathy:
causes proximal and girdle weakness – difficulty in elevating the arms and standing from kneeling, walking up stairs.
EMG – normal or mildly myopathic. No fibrillations.
Biopsies – atrophy of type 2B fibers – no necrosis or inflammatory cells.
Serum CPK and Aldolase – Normal
Discontinuation leads to gradual improvement
-
Critical Illness Myopathy – Acute Steroid Myopathy: myosin – depleted myopathy
Severe, acute, in critically ill patients. Acute quadriplegia.
May be associated with the use of neuromuscular blocking agents.
Severe weakness usually manifests when the systemic illness subsides.
Recovery long
Serum CPK is elevated
EMG – myopathic pattern and fibrillations
Muscle biopsy – necrosis and vacuolation type 2 fibers. Loss of myosin filaments IS the feature.
May be accompanied by myoglobinuria and renal failure.
* Hypothyroid Myopathy:
Diffuse myalgia, stiffness, slowness of contraction and relaxation – percussion myoedema, myokymia
CPK elevated – often markedly
- Chronic Thyrotoxic myopathy: CPK normal or reduced
- Statin induced myopathy: CPK raised – often no cliincal manifestation.
- DMD: The serum CK values are 25 to 200 times normal, which, with the EMG and muscle biopsy findings, help exclude spinal muscular atrophy. The EMG shows fibrillations, positive waves, low-amplitude and brief polyphasic motor unit potentials, and, sometimes, highfrequency discharges.
- Cochicine: causes mild subacute proximal myopathy, but may also cause an acute necrotising myopathy (often associated with renal fialure) may be ssoicated with sensory distal loss – therefore myoneuropathy which is refelcted in muscle biopsy as well
CPK normal or elevated. - Alcohol myopathy – associated with severe hypokalaemia – treat with KCL, if acute alcohol myopathy – severe pain, edema of muscles, renal damage – CPK elevated.
שתי תשובות נכונות- א+ ג
Colchicine, used widely in the treatment of gout, often gives rise to a mild subacute proximal muscular weakness but has also produced an acute necrotizing myopathy**.
Most instances of the latter have occurred in patients with a degree of renal failure, which allows accumulation of the drug (even though the drug is metabolized predominantly by the liver).
In rare instances the myopathy has affected the cranial musculature and the diaphragm.
Many cases also show clinical or electrophysiologic **evidence of a
Polyneuropathy**, leading to the term **colchicine myoneuropathy*. The reflexes are diminished and there is mild distal sensory loss.
The serum CK concentration may be elevated or normal.
The muscle biopsy shows elements of both myopathic and neuropathic disease, with the special feature in muscle of rimmed vacuoles on the Gomori trichrome stain that are more central in the muscle fibers than those seen with inclusion body myositis.
Weakness resolves in a matter of days or weeks when the drug is discontinued, but the neuropathic features may remain.
Other drugs that cannot be compactly summarized
but may produce a toxic myopathy or neuromyopathy
include amiodarone, chloroquine, and hydroxychloroquine
אין טיפול
Inclusion body myositis
- It is characterized by a steadily progressive, painless muscular weakness and modest atrophy, which is usually distal in the arms and both proximal and distal in the legs.
- In approximately 20 percent of cases, the disease begins with focal weakness of the quadriceps, finger or wrist flexors, or lower leg muscles on one or both sides, and gradually spreads to other muscle groups after many months or years. Selective weakness of the flexor pollicis longus is a particularly characteristic pattern of involvement, and isolated quadriceps weakness or neck extensor weakness should also bring the diagnosis to mind, although IBM is not the exclusive cause of these patterns. In most patients, the deltoids are spared and the thumb flexors are Weak, the opposite pattern to PM and DM. The tendon reflexes are normal initially but diminish in about half the patients, especially the knee jerks, as the disease progresses. Interestingly, the knee jerks may be depressed or lost even without much in the way of quadriceps weakness; this is not the case in PM, in which the reflexes are spared until the muscle is extremely weak. Dysphagia is common, Selective or asymmetric involvement of distal muscles, when it occurs, erroneously suggests the diagnosis of motor neuron disease (the reflexes are not, however, enhanced as they are in ALS).
- The CK is normal or slightly elevated, generally showing lower levels than in cases of PM with comparable amounts of weakness. EMG abnormalities are much like those found in PM, as discussed earlier. In addition, a small proportion of IBM patients display a more typically neuropathic EMG pattern, mainly with long-duration
polyphasic potentials because of the chronicity of the disease, in the distal limb muscles. However, the EMG changes tend to be restricted to weakened muscles, a distinction from ALS. - The diagnosis depends on the clinical features and is supported by the muscle biopsy. There are structural abnormalities of muscle fibers and inflammatory Changes. The latter are identical to but usually of lesser severity than those observed in idiopathic PM. (The infiltrating cells are mainly T cells of the CDS type.) The denominative finding is of intracytoplasmic, subsarcolemmal vacuoles and eosinophilic inclusions in both the cytoplasm and nuclei of degenerating muscle fibers. The vacuoles contain, and are rimmed by, basophilic granular material “rimmed vacuoles”.
Of clinical utility has been the recent introduction of testing for the earlier mentioned cytosolic antibodies (anti-cN1; NT5C1A) that are found in two-thirds of patients with IBM. - IBM has not responded in any consistent fashion to treatment with corticosteroids or other immunosuppressive drugs. In a few cases there has been brief improvement in response to Mg, especially in weakened muscles involved in swallowing, but the gains have been unsustained The disease in most patients is relentlessly progressive
over many years, sometimes very slowly, and no method of treatment has so far altered the long-term prognosis. Sometimes, the process remains fairly restricted in scope.
bimagrumab, an antibody directed to signaling of TGF-β receptor, has shown some improvement of muscle mass but a definitive clinical demonstration of effect has not been tested
מהו הממצא האופייני בביופסיית שריר של
IBM
Rimmed vacuoles
Inclusion body myositis
- It is characterized by a steadily progressive, painless muscular weakness and modest atrophy, which is usually distal in the arms and both proximal and distal in the legs.
- In approximately 20 percent of cases, the disease begins with focal weakness of the quadriceps, finger or wrist flexors, or lower leg muscles on one or both sides, and gradually spreads to other muscle groups after many months or years. Selective weakness of the flexor pollicis longus is a particularly characteristic pattern of involvement, and isolated quadriceps weakness or neck extensor weakness should also bring the diagnosis to mind, although IBM is not the exclusive cause of these patterns. In most patients, the deltoids are spared and the thumb flexors are Weak, the opposite pattern to PM and DM. The tendon reflexes are normal initially but diminish in about half the patients, especially the knee jerks, as the disease progresses. Interestingly, the knee jerks may be depressed or lost even without much in the way of quadriceps weakness; this is not the case in PM, in which the reflexes are spared until the muscle is extremely weak. Dysphagia is common, Selective or asymmetric involvement of distal muscles, when it occurs, erroneously suggests the diagnosis of motor neuron disease (the reflexes are not, however, enhanced as they are in ALS).
- The CK is normal or slightly elevated, generally showing lower levels than in cases of PM with comparable amounts of weakness. EMG abnormalities are much like those found in PM, as discussed earlier. In addition, a small proportion of IBM patients display a more typically neuropathic EMG pattern, mainly with long-duration
polyphasic potentials because of the chronicity of the disease, in the distal limb muscles. However, the EMG changes tend to be restricted to weakened muscles, a distinction from ALS. - The diagnosis depends on the clinical features and is supported by the muscle biopsy. There are structural abnormalities of muscle fibers and inflammatory Changes. The latter are identical to but usually of lesser severity than those observed in idiopathic PM. (The infiltrating cells are mainly T cells of the CDS type.) The denominative finding is of intracytoplasmic, subsarcolemmal vacuoles and eosinophilic inclusions in both the cytoplasm and nuclei of degenerating muscle fibers. The vacuoles contain, and are rimmed by, basophilic granular material “rimmed vacuoles”.
Of clinical utility has been the recent introduction of testing for the earlier mentioned cytosolic antibodies (anti-cN1; NT5C1A) that are found in two-thirds of patients with IBM. - IBM has not responded in any consistent fashion to treatment with corticosteroids or other immunosuppressive drugs. In a few cases there has been brief improvement in response to Mg, especially in weakened muscles involved in swallowing, but the gains have been unsustained The disease in most patients is relentlessly progressive
over many years, sometimes very slowly, and no method of treatment has so far altered the long-term prognosis. Sometimes, the process remains fairly restricted in scope.
bimagrumab, an antibody directed to signaling of TGF-β receptor, has shown some improvement of muscle mass but a definitive clinical demonstration of effect has not been tested
אין טיפול יעיל
Inclusion body myositis
- It is characterized by a steadily progressive, painless muscular weakness and modest atrophy, which is usually distal in the arms and both proximal and distal in the legs.
- In approximately 20 percent of cases, the disease begins with focal weakness of the quadriceps, finger or wrist flexors, or lower leg muscles on one or both sides, and gradually spreads to other muscle groups after many months or years. Selective weakness of the flexor pollicis longus is a particularly characteristic pattern of involvement, and isolated quadriceps weakness or neck extensor weakness should also bring the diagnosis to mind, although IBM is not the exclusive cause of these patterns. In most patients, the deltoids are spared and the thumb flexors are Weak, the opposite pattern to PM and DM. The tendon reflexes are normal initially but diminish in about half the patients, especially the knee jerks, as the disease progresses. Interestingly, the knee jerks may be depressed or lost even without much in the way of quadriceps weakness; this is not the case in PM, in which the reflexes are spared until the muscle is extremely weak. Dysphagia is common, Selective or asymmetric involvement of distal muscles, when it occurs, erroneously suggests the diagnosis of motor neuron disease (the reflexes are not, however, enhanced as they are in ALS).
- The CK is normal or slightly elevated, generally showing lower levels than in cases of PM with comparable amounts of weakness. EMG abnormalities are much like those found in PM, as discussed earlier. In addition, a small proportion of IBM patients display a more typically neuropathic EMG pattern, mainly with long-duration
polyphasic potentials because of the chronicity of the disease, in the distal limb muscles. However, the EMG changes tend to be restricted to weakened muscles, a distinction from ALS. - The diagnosis depends on the clinical features and is supported by the muscle biopsy. There are structural abnormalities of muscle fibers and inflammatory Changes. The latter are identical to but usually of lesser severity than those observed in idiopathic PM. (The infiltrating cells are mainly T cells of the CDS type.) The denominative finding is of intracytoplasmic, subsarcolemmal vacuoles and eosinophilic inclusions in both the cytoplasm and nuclei of degenerating muscle fibers. The vacuoles contain, and are rimmed by, basophilic granular material “rimmed vacuoles”.
Of clinical utility has been the recent introduction of testing for the earlier mentioned cytosolic antibodies (anti-cN1; NT5C1A) that are found in two-thirds of patients with IBM. - IBM has not responded in any consistent fashion to treatment with corticosteroids or other immunosuppressive drugs. In a few cases there has been brief improvement in response to Mg, especially in weakened muscles involved in swallowing, but the gains have been unsustained The disease in most patients is relentlessly progressive
over many years, sometimes very slowly, and no method of treatment has so far altered the long-term prognosis. Sometimes, the process remains fairly restricted in scope.
bimagrumab, an antibody directed to signaling of TGF-β receptor, has shown some improvement of muscle mass but a definitive clinical demonstration of effect has not been tested
Rimmed vacuoles
Inclusion body myositis
- It is characterized by a steadily progressive, painless muscular weakness and modest atrophy, which is usually distal in the arms and both proximal and distal in the legs.
- In approximately 20 percent of cases, the disease begins with focal weakness of the quadriceps, finger or wrist flexors, or lower leg muscles on one or both sides, and gradually spreads to other muscle groups after many months or years. Selective weakness of the flexor pollicis longus is a particularly characteristic pattern of involvement, and isolated quadriceps weakness or neck extensor weakness should also bring the diagnosis to mind, although IBM is not the exclusive cause of these patterns. In most patients, the deltoids are spared and the thumb flexors are Weak, the opposite pattern to PM and DM. The tendon reflexes are normal initially but diminish in about half the patients, especially the knee jerks, as the disease progresses. Interestingly, the knee jerks may be depressed or lost even without much in the way of quadriceps weakness; this is not the case in PM, in which the reflexes are spared until the muscle is extremely weak. Dysphagia is common, Selective or asymmetric involvement of distal muscles, when it occurs, erroneously suggests the diagnosis of motor neuron disease (the reflexes are not, however, enhanced as they are in ALS).
- The CK is normal or slightly elevated, generally showing lower levels than in cases of PM with comparable amounts of weakness. EMG abnormalities are much like those found in PM, as discussed earlier. In addition, a small proportion of IBM patients display a more typically neuropathic EMG pattern, mainly with long-duration
polyphasic potentials because of the chronicity of the disease, in the distal limb muscles. However, the EMG changes tend to be restricted to weakened muscles, a distinction from ALS. - The diagnosis depends on the clinical features and is supported by the muscle biopsy. There are structural abnormalities of muscle fibers and inflammatory Changes. The latter are identical to but usually of lesser severity than those observed in idiopathic PM. (The infiltrating cells are mainly T cells of the CDS type.) The denominative finding is of intracytoplasmic, subsarcolemmal vacuoles and eosinophilic inclusions in both the cytoplasm and nuclei of degenerating muscle fibers. The vacuoles contain, and are rimmed by, basophilic granular material “rimmed vacuoles”.
Of clinical utility has been the recent introduction of testing for the earlier mentioned cytosolic antibodies (anti-cN1; NT5C1A) that are found in two-thirds of patients with IBM. - IBM has not responded in any consistent fashion to treatment with corticosteroids or other immunosuppressive drugs. In a few cases there has been brief improvement in response to Mg, especially in weakened muscles involved in swallowing, but the gains have been unsustained The disease in most patients is relentlessly progressive
over many years, sometimes very slowly, and no method of treatment has so far altered the long-term prognosis. Sometimes, the process remains fairly restricted in scope.
bimagrumab, an antibody directed to signaling of TGF-β receptor, has shown some improvement of muscle mass but a definitive clinical demonstration of effect has not been tested
מחלת
GNE myopathy
אינה מאופיינת ב:
1. חולשת מכופפי אצבעות ידיים
2. foot drop בשלב מוקדם של המחלה
3. quadriceps sparing
4. הימצאות פולינוירופתיה בבדיקת EMG
5. מועברת בתורשה אוטוזומלית רצסיבית
בנונקה אין פולינוירופתיה באי אמ ג’י
תיאור של מטופלתעם חולשת צוואר, קושי בבליעה, חולשת שרירים ,
CPK5000 ,
ללאהפרעהדרמטולוגית.עשוביופסיה–מה יצא?
1. widespread destruction of segemnts
2. intracytoplasmic inclusions
3. Perifasicularatrophy
4. eosinophilic infiltrate
widespread destruction of segemnts of fibers with infalmattion reaction
The principal changes in idiopathic PM consist of widespread destruction of segments of muscle fibers with an inflammatory reaction, that is, phagocytosis of muscle fibers by mononuclear cells and infiltration with a varying number of lymphocytes and lesser numbers of other mononuclear and plasma cells. Evidence of regenerative activity of muscle, mainly in the form of proliferating sarcolemmal nuclei, basophilic (RNA-rich) sarcoplasm, and new myofibrils, is evident in damaged regions. Many of the residual muscle fibers are small, with increased numbers of sarcolemmal nuclei. Some of the small fibers are found in clusters, the result of splitting of regenerating fibers.
In PM, there are a large number of activated T
cells, mainly of the CDS class, whereas B cells are sparse.
גבר לאחר מחלה ויראלית, חולשה פרוקסימלית, דיבור נזאלי
CPK 4500, ANA חיובי
בביופסיה דלקת אנדומזיאלית
מה האבחנה?
1. פולימיוזיטיס
2. דרמטומיוזיטיס
3. מיאסטנה
פולימיוזיטיס
In the strictest sense, this is an idiopathic subacute or chronic and symmetrical weakness of proximal limb and trunk muscles without dermatitis. The pattern of weakness is similar and most comments pertaining to DM given above also apply to PM. The difference is the rash and associated skin changes, which by definition are absent in this disorder. In question is the frequency of this disorder as an independent entity, with some authorities questioning its existence.
In both PM and DM, there may be involvement of organs other than muscle. In a surprising number of our cases of PM (and DM), cardiac abnormalities have been observed and in a small proportion of these, sudden death has occurred. The cardiac manifestations have taken the form of relatively minor electrocardiographic (ECG) changes, but several patients have had arrhythmias with clinical consequences. Among the fatal cases, about half have shown necrosis of myocardial fibers at autopsy, usually with only modest inflammatory changes. Interstitial lung disease is another known association in a few cases; its frequency ranges from 10 to 47 percent in different series and up to 70 percent in one subtype with anti-Jo antibodies (see further on under “Laboratory Diagnosis of PM and DM”), but the lower figure is probably correct. Exceptionally, there is a low-grade fever, especially if joint pain coexists.
באילו מהמחלות יכול האנזים
CK
לשמש למעקב אחר תגובה לטיפול?:
א. Polymyositis
ב. Steroid myopathy
ג. Inclusion body Myositis
ד. Limb girdle muscular dystrophy
פולימיוזיטיס
אישה בת 70 עם פריחה אדומה סביב העיניים, על החזה ובאצבעות הידיים, מתלוננת על חולשת שרירים. מה אינו מתאים למצבה?
1. חולשה פרוקסימלית של 4 גפיים
2. CPK מוגבר במאוד עד אלפים
3. EMG- דהנרבציה של סיבי שריר
4. EMG גיוס ירוד של יחידות שריר
5. בביופסיית שריר אטרופייה פריפסיקולרית
peri-fascicular atrophy
בת 40 עם הופעה חדשה של קושי לעלות במדרגות ולהסתרק, יש שינויים בעור בלחיים,
CPK מעט מוגבר
איזה ממצא בפתולוגיה יחייב חיפוש אחר ממאירות:
1. perifascicular infiltration
2. eosinophilic infiltration
3. fiber necrosis
perifascicular infiltration
In DM, there are several other distinctive histopathologic
changes. In contrast to the evident necrosis of single fibers of PM, DM is characterized by perifascicular muscle fiber atrophy (referring to changes at the periphery of a fascicle, for reasons noted below). Moreover, the inflammatory infiltrates in DM predominate in the perimysial connective tissue, whereas in PM they are
scattered throughout the muscle and are most prominent in relation to the muscle fiber membrane and the endomysium.
The muscle lesions in dermatomyositis of childhood are similar to those of the adult form, only greatly accentuated. In a biopsy sample, the diagnosis can be inferred from the perifascicular pattern of degeneration and atrophy of muscle fibers.
Even more distinctive of DM are microvascular changes in muscle. Endothelial alterations (tubular aggregates in the endothelial cytoplasm) and occlusion of vessels by fibrin thrombi may be appreciated, with associated zones of infarction. The same vascular changes underlie the lesions in the connective tissue of skin, subcutaneous tissue, and gastrointestinal tract when they are present.
in DM, the percentage of B cells at all sites is significantly higher than it is in PM.
מחלת
myotonic dystrophy type 1
אינה מאופיינת ב:
1. פטוזיס וחולשת שרירי פנים
2. התקרחות
3. דלדול שרירים טמפורלים
4. קושי בדיבור בשל מיוטוניה של הלשון
5. חולשת שרירים דיסטליים
6. חולשת שרירי נשימה
7. אמא לרוב אסימפטומטית בשל תורשה בתאחיזה לכרומוזום X
הורשה של מיוטוניק דיסטרופי הינה דומיננטית. הילד יותר חולה מאמא בגלל
anticipation
בן 46 נבדק עקב חולשת שרירים מתקדמת. בבדיקה: הקרחה פרונטלית, פטוזיס, דיבור היפופוני וקושי
בשחרור היד לאחר לחיצתה על ידי הבודק.
איזה ממצא נוסף עלול להתפתח בשלבים מתקדמים של המחלה:?
א. Bronchiectasis
ב. Shortened PR interval on EKG
ג. Glaucoma
ד. Diabetes Insipidus
א-חולשת סרעפת והיפוונטילציה שגורמת לברונכואקטזיות וברוניכיטיס הם סיבוכים מאוחרים
קצת על המסיחים האחרים-
ב. PR elongation and not shortend
ג-לא גלאקומה –קטרקט
ד-סיכוי גבוה יותר לסוכרת, וברוב המקרים תהיה אי סבילות לגלוקוז (בהעמסת סוכר)
בן 40 עם אטרופיה טמפורלית , חולשתטרייספס, וירידה בפוריות . מה עוד יהיה לו ?
1. ירידה בCMAPדיסטלי
2. Retinitis pigmentosa
3. ירידה קוגניטיבית מוקדמת
4. מעורבות לבבית מאופיינת בעיקר על ידי טרשת עורקים
ירידה קוגניטיבית מוקדמת
Mild to moderate degrees of developmental cognitive delay are common in DMl, and the brain weight in several of our patients was 200 g less than that in normal individuals of the same age. Late in adult life, some patients become suspicious, argumentative, and forgetful.
במי תתכן ירידה קוגניטיבית?
1. myotonic dystrophy
2. FSH
3. friedriech ataxia
4. SCA 3
myotobuc dystrophy
Mild to moderate degrees of developmental cognitive delay are common in DMl, and the brain weight in several of our patients was 200 g less than that in normal individuals of the same age. Late in adult life, some patients become suspicious, argumentative, and
forgetful.
No cognitive involvement in FSH, Friedrich or Machado-joseph
- Friedrich: Although mentation is generally preserved, emotional lability has been sufficiently prominent to provoke Comment
-
SCA3: The disorder is characterized by an autosomal dominant pattern of inheritance and by a slowly progressive ataxia beginning in adolescence or early adult life in association with hyperreflexia, extrapyramidal features, dystonia, bulbar signs, distal motor weakness, and ophthalmoplegia.
There is usually no impairment of intellect.
CAG repeats in Ataxin gene
באיזו מהמחלות הבאות יש לחלק מן החולים הפרעה קוגניטיבית?
1. myotonic dystrophy
2. juvenile SMA (Kugelberg wellander)
3. SCA 3 (Machado joseph)
4. Friedreich’s ataxia
5. Facioscapulohumeral muscular dystrophy
myotobuc dystrophy
Mild to moderate degrees of developmental cognitive delay are common in DMl, and the brain weight in several of our patients was 200 g less than that in normal individuals of the same age. Late in adult life, some patients become suspicious, argumentative, and
forgetful.
No cognitive involvement in FSH, Friedrich or Machado-joseph
- Friedrich: Although mentation is generally preserved, emotional lability has been sufficiently prominent to provoke Comment
-
SCA3: The disorder is characterized by an autosomal dominant pattern of inheritance and by a slowly progressive ataxia beginning in adolescence or early adult life in association with hyperreflexia, extrapyramidal features, dystonia, bulbar signs, distal motor weakness, and ophthalmoplegia.
There is usually no impairment of intellect.
CAG repeats in Ataxin gene
איזה שריר מהבאים מעורב הכי פחות ב-
myotonic dystrophy type 1
1. masseter
2. sternocleidomastoid
3. abductor pollicis brevis
4. iliopsoas
5. tibialis anterior
Iliopsoas
Myotonic dystrophy 1
autosomal dominant pattern of inheritance with a high level of penetrance, CTG repeat in myotonin protein kinase gene.
special topography of the muscle atrophy, associated obvious myotonia, and occurrence of dystrophic changes in nonmuscular tissues (lens of eye, testicle and other endocrine glands, skin, esophagus, heart, and, in some cases, the cerebrum).
Certain muscles, the levator palpebrae, facial, masseter, sternocleidomastoid, and forearm, hand, and pretibial muscles, are consistently involved in the dystrophic process.
In the common early adult form of the disease, the small muscles of the hands along with the extensor muscles of the forearms are often the first to become atrophied. In other cases, ptosis of the eyelids and thinness and slackness of the facial muscles may be the earliest signs, preceding other muscular involvement by many
years. Atrophy of the masseters leads to narrowing of the lower half of the face, and the mandible is slender and mal positioned so that the teeth do not occlude properly. This, along with the ptosis, frontal baldness, and wrinkled forehead, imparts a distinctive physiognomy that, once seen, can be recognized at a glance (“hatchet“ face). The sternocleidomastoids are almost invariably thin and weak and are associated with an exaggerated forward curvature of the neck (“swan neck”). Atrophy of the anterior tibial muscle groups, leading to foot-drop, is an early sign in some families. Pharyngeal and laryngeal weakness results in a weak, monotonous, nasal voice. The uterine muscle may be weakened, interfering with normal parturition, and the esophagus is often dilated because of loss of muscle fibers in the striated as well as smooth muscle parts. Megacolon occurs in some patients. Diaphragmatic weakness and alveolar hypoventilation, resulting in chronic bronchitis and bronchiectasis, are common late features, as are cardiac abnormalities; the latter are most often a result of disease of the conducting apparatus, giving rise to bradycardia and a prolonged P-R interval. The disease progresses slowly, with gradual involvement of the proximal muscles of the limbs and muscles of the trunk. Tendon reflexes are lost or much reduced. Contracture is rarely seen, and the thin, flattened hands are consequently soft and pliable. Most patients are confined to a wheelchair or bed within 15 to 20 years of the first signs, and death occurs before the normal age from pulmonary infection, heart block, or heart failure.
- In DM2 – PROMM- Proximal muscle weakness, cataracts, myotonia
- The muscle hypertrophy that is characteristic of myotonia congenita is not a feature of myotonic dystrophy.
לא תהיה היפרטרופיה של הסובכים
Iliopsoas
Myotonic dystrophy 1
autosomal dominant pattern of inheritance with a high level of penetrance, CTG repeat in myotonin protein kinase gene.
special topography of the muscle atrophy, associated obvious myotonia, and occurrence of dystrophic changes in nonmuscular tissues (lens of eye, testicle and other endocrine glands, skin, esophagus, heart, and, in some cases, the cerebrum).
Certain muscles, the levator palpebrae, facial, masseter, sternocleidomastoid, and forearm, hand, and pretibial muscles, are consistently involved in the dystrophic process.
In the common early adult form of the disease, the small muscles of the hands along with the extensor muscles of the forearms are often the first to become atrophied. In other cases, ptosis of the eyelids and thinness and slackness of the facial muscles may be the earliest signs, preceding other muscular involvement by many
years. Atrophy of the masseters leads to narrowing of the lower half of the face, and the mandible is slender and mal positioned so that the teeth do not occlude properly. This, along with the ptosis, frontal baldness, and wrinkled forehead, imparts a distinctive physiognomy that, once seen, can be recognized at a glance (“hatchet“ face). The sternocleidomastoids are almost invariably thin and weak and are associated with an exaggerated forward curvature of the neck (“swan neck”). Atrophy of the anterior tibial muscle groups, leading to foot-drop, is an early sign in some families. Pharyngeal and laryngeal weakness results in a weak, monotonous, nasal voice. The uterine muscle may be weakened, interfering with normal parturition, and the esophagus is often dilated because of loss of muscle fibers in the striated as well as smooth muscle parts. Megacolon occurs in some patients. Diaphragmatic weakness and alveolar hypoventilation, resulting in chronic bronchitis and bronchiectasis, are common late features, as are cardiac abnormalities; the latter are most often a result of disease of the conducting apparatus, giving rise to bradycardia and a prolonged P-R interval. The disease progresses slowly, with gradual involvement of the proximal muscles of the limbs and muscles of the trunk. Tendon reflexes are lost or much reduced. Contracture is rarely seen, and the thin, flattened hands are consequently soft and pliable. Most patients are confined to a wheelchair or bed within 15 to 20 years of the first signs, and death occurs before the normal age from pulmonary infection, heart block, or heart failure.
- In DM2 – PROMM- Proximal muscle weakness, cataracts, myotonia
- The muscle hypertrophy that is characteristic of myotonia congenita is not a feature of myotonic dystrophy.
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בחור צעיר מופיע עם חולשה דיסטלית וקושי לעמוד על קצות האצבעות. לאחותו חולשה בחגורת האגן. איזה חלבון פגוע?
1. emerin
2. dysferlin
3. dystrophin
dysferlin
Limb girdle dystrophy 2B has been linked to the same chromosomal locus and it also lacks the dysferlin protein. It is
also striking that different family members with the same dysferlin mutation can have disease onset in either a proximal (LGMD) or distal (Miyoshi) pattern, suggesting that additional factors modify the pattern of weakness produced by dysferlin deficiency/
בן 17 פונה בשל חולשת שרירים דיסטלית שהחלה בגסטרוקנמיוס וגרמה לחוסר יכולת לעמוד על הבהונות וקושי בעלייה במדרגות. ההורים בני דודים ובבדיקת אחים של החולה נמצאה אחות בת 12 עם סימני חולשה בחגורת הכתפיים ובאגן. באיזה גן מהחלבונים הבאים תימצא מוטציה?
1. desmin
2. emerin
3. capain
4. dysferlin
5. merosin
dysferlin
Limb girdle dystrophy 2B has been linked to the same chromosomal locus and it also lacks the dysferlin protein. It is
also striking that different family members with the same dysferlin mutation can have disease onset in either a proximal (LGMD) or distal (Miyoshi) pattern, suggesting that additional factors modify the pattern of weakness produced by dysferlin deficiency/
באיזו מחלה אופיינית חולשת שרירים דיסטלית?
א. Miyoshi Myopathy (LGMB2)
ב. Emery-Dreifuss muscular Dystrophy
ג. Becker Muscular Dystrophy
ד. Myofibrillar myopathy
מיושי מיופטי
מחלת
FSHD
מאופיינת ב:
1. חולשת שריר כתף שמערבת בעיקר את הדלטואיד
2. חולשה סימטרית של שרירי הגפיים
3. חוסר מעורבות של שריר הטיביאליס אנטריור
4. דלדול שרירי קיר הבטן
5. חוסר סיפור משפחתי
דלדול שרירי קיר הבטן
מטופל עם קושי בהרמת ידיים ובשריקה. איזה שינוי גנטי מתאים?
1.CTG
2.4q
3.שרשראות אלנין
כרומוזום
4q
מטופל עםדילדולשל הצוואר , ללא אטרופיה , ללא סימנים פירמידליים , (ללאפסיקולאציות) לאיזה גן יכול להיות קשור ?
1. calpain 3(LGMD 2A)
2. Rapsyn
3. Ryanodine
4. Superoxide
Ryanodine
Several recent series have suggested that mutations in RYR1 that encode for ryanodine receptor may be a common cause of late onset axial myopathy and neck extensor weakness-bent spine syndrome. Mutations in RYR1 are more commonly associated with the central core congenital myopathy or malignant hyperthermia.
The major types of progressive muscular dystrophies, when advanced, usually affect the anterior neck muscles severely. Syringomyelia, spinal accessory neuropathy, some form of meningoradiculitis, and loss of anterior horn cells in conjunction with systemic lymphoma or carcinoma may differentially paralyze the various neck muscles.
חולה אונקולוגי מקבל טיפול בסטרואידים ומפתח חולשת שרירים . מה לא מוריד סיכוןלמיופתיה?
1. ירידה במינון סטרואידים
2. ירידה במשך סטרואידים
3. Dexacortisoneinstead of hydrocortisone
4. טיפול יום כן יום לא
Dexacortisoneinstead of hydrocortisone
אישה בת 50 עם דיסליפידמיה מתלוונת על חודש עם חולשת שרירים פרוגרסיבית. החלה לפני חצי שנה טיפול בסטטינים וכעת יש ירידה ניקרת במשקל.
CPK- סביב 5000
ביופסיית שריר הראתה
necrotic autoimmune myopathy
מה הסיבה לכך?
1. breast cancer
2. statin treatment
3. anti SRP autoimmune disorder
4. idiopathic
5. כל הנ”ל
כל התשובות נכונות
קצת על
LGMD
