פרק 45 chapter 45 disease of muscle Flashcards

Question

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

Answer 1

דיסטרופין האישה בשאלה היא asymptomatic carrier של דושן

Answer 2

קונטרוקטורות בדושן אין קרדיומיופתיה אלא אריטמיות משניות לפיברוזיס לבבי. ויש להם עיכוב התפתחותי עם איי קיו נמוך אבל אין מהלך פרוגרסיבי של ירידה קוגניטיבית.

Answer 3

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 2. **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 3. **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*

Answer 4

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

Answer 5

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 2. **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

Answer 6

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

Answer 7

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

Answer 8

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

Answer 9

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

Answer 10

צורך בקוצב בשל הפרעות הולכה בלב הקטע עם המרפקים- חוסר יכולת ליישר לא לכופף

Answer 11

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).

Answer 12

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).

Answer 13

אוקי אז זה נכון שיש גם בדושן.. אבל באמרי דרייפוס יש הכי הרבה

Answer 14

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)

Answer 15

מוצא פרסי אינו תומך באבחנה- הולך יותר עם nonaka (GME/hereditary IBM)

Answer 16

Perifasicullar atrophy= dermatomyositis

Answer 17

בפומפה- . אלקטרומיוגרפיה של שרירים פאראספינליים- אינו תקין EMG

Answer 18

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**

Answer 19

acid maltase **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** המסיחים האחרים- מיופוספוריזל זה מקארדל ברנצ'ינג אנזים- פוליגלוקוזן

Answer 20

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

Answer 21

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

Answer 22

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

Answer 23

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

Answer 24

**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

Answer 25

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

Answer 26

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.

Answer 27

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.

Answer 28

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*.

Answer 29

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.

Answer 30

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.

Answer 31

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.

Answer 32

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 2. **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.

Answer 33

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

Answer 34

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

Answer 35

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

Answer 36

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

Answer 37

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

Answer 38

בנונקה אין פולינוירופתיה באי אמ ג'י

Answer 39

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.

Answer 40

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.

Answer 41

פולימיוזיטיס

Answer 42

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.

Answer 43

הורשה של מיוטוניק דיסטרופי הינה דומיננטית. הילד יותר חולה מאמא בגלל anticipation

Answer 44

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)

Answer 45

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.

Answer 46

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

Answer 47

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

Answer 48

**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.

Answer 49

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. .

Answer 50

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/

Answer 51

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/

Answer 52

מיושי מיופטי

Answer 53

דלדול שרירי קיר הבטן

Answer 54

כרומוזום 4q

Answer 55

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.

Answer 56

Dexacortisone instead of hydrocortisone

Answer 57

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פרק 45 chapter 45 disease of muscle Flashcards

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