פרק 43 Chapter 43: Diseases of the Peripheral Nerves Flashcards

Question

. תיאור של קליניקה של רפסום עם ממצא של ח.פיטנית מוגברת. מה לא נכון? 1. חרשות 2. עיוורון 3. קרדיומיופתיה 4. ירידה קוגניטיבית 5. עליה בחלבון בCSF

Answer 1

ירידה קוגניטיבית אינה חלק מרפסום

Answer 2

פלזמה פרזיס או IVIG **DADS**-distal acquired demyelinating symmetrical neuropathy: distal sensory and sometimes motor, disturbances and **greatly prolonged distal latencies** in most patients, and **two-thirds have an associated IgM monoclonal gammopathy** with **kappa** light chain component; the illness **responds poorly to Treatment**, aligning it clinically in some respects with the anti-MAG neuropathies but in most clinical and electrophysiologic features appearing to be a **variant of CIDP**. **Treatment is the same as GBS CIDP** high doses of gamma globulin or plasma exchange. after a while the infusions must be repeated to maintain clinical improvement

Answer 3

נוירופתיה פמורלית **Femoral** : **L2, 3, 4** * Nerve splits into anteiror and posterior divisions- 1. **Anterior** – **pectineus and sartorius (flexion of hip)** – **sensation anteromedial surface of thigh**. 2. **Posterior motor** innervation to **quadriceps** and **cutaneous innervation to medial side of leg from knee to internal malleolus** * Femoral nerve weakness- weakness of **quads** – extension of knee, wasting and difficulty to stabilise Knee. **Knee jerk abolished**, If the nerve lesion is proximal to the branches of the **iliacus and psoas** muscles – weakness of hip flexion. * To decide between **femoral neuropathy and L3 – check for involvement of obturator** (hip adductor weakness). The main effects of **upper lumbar plexus lesions** are weakness of **flexion(*femoral nerve*) and adduction(*obturator nerve*) of the thigh and extension of the leg**, with **sensory loss over the anterior thigh and leg**; these effects must be distinguished from the symptoms and signs of femoral neuropathy

Answer 4

Tomacualle - sausage shape. **Hereditary Neuropathy With Pressure Palsies (HNPP, PMP22 Deletion)** multiple recurrent local neuropathies, caused by a **deletion** of the **PMP22** gene, *duplicated in the previously described CMT1A*. In both the PMP22 gene is *functionally normal* but the *total amount of the protein is abnormal*. CMT1A the gene is duplicated on one chromosome, thereby increasing the total PMP22 protein; by contrast, in **HNPP, the gene is deleted so that the PMP22 protein is at approximately half-normal levels**. HNPP is transmitted as a **dominant trait**. In these individuals, the focal neuropathies and plexopathies are generally **not painful**. Focal nerve lesions are often **provoked by slight or even brief compression**. In addition to recurrent focal nerve palsies, most individuals with HNPP have an **underlying chronic but slowly progressive demyelinating sensorimotor neuropathy** that is mild on clinical examination (e.g., not all cases show areflexia). **Electrophysiologic studies are abnormal**, but may be only subtly so, with some **slowing of conduction and distal motor and sensory nerve abnormalities**, particularly across sites of compression. **Nerve biopsies** from these patients are most remarkable for the presence of localized nerve sheath thickening with duplication of the myelin lamellae (so-called **tomaculae**, meaning sausage shaped).

Answer 5

EMG reduced conduction velocity and conduction block like that in demyelinating CSF cytoalbuminologoc dissociation

Answer 6

MADSAM (multifocal aquired demyelination sensory and motor neuropathy) איך שוללים את שאר המסיחים: MMNis only motor Aidp and cidp have high protein in the CSF. פירוט: --- Several polyneuropathies that share many of the features of CIDP have been delineated on the basis of unique clinical, immune, or electrophysiologic attributes. These include particularly multifocal motor neuropathy (**MMN**) and **multifocal conduction block** (also called **MADSAM**). The MADSAM has as its main feature **a block of mixed nerve conduction at focal sites in a limited number of nerves**. In *multifocal motor neuropathy, only blocks in motor nerve conduction are evident*. The distinction between these two entities has been difficult. There are similarities in clinical features and response to treatment, but there is utility in separating them. **Multifocal motor neuropathy**, is associated in half of cases with a **particular IgM antibody, anti-GMI** directed against a **ganglioside component of peripheral myelin** Multifocal motor neuropathy and motor conduction block **predominate in men**. They usually begin with an acute or subacute **motor mononeuropathy**, manifest, for example, as weakness of the wrist or foot-drop, and are often **joined insidiously by another** focal motor palsy. The **process is painless, unlike vasculitic mononeuritis multiplex,** involves the nerve incompletely, and, in its usual form, is **unaccompanied by any sensory symptoms** such as paresthesias or numbness. Despite the initially demyelinating character of the disorder, there is almost always **atrophy of the weakened muscle** within months and there may be a **few fasciculations**, thus simulating ALS. Nevertheless, the **weakness tends to be disproportionate to atrophy**. Usually, the **tendon reflex is lost or muted** in an affected region, but for unexplained reasons, some patients have one or more brisk reflexes. Our experience has been that this latter reflex change does not reach the point of appearing "pathologic" and that clonus and Babinski signs are categorically not part of the illness, as they are in ALS. ***When there is an association of the motor features with sensory symptoms*** or sensory loss and there is slowing of sensory conduction in regions of motor conduction block (**multifocal conduction block**), the acronym **MADSAM **(multifocal acquired demyelinating sensory and motor neuropathy) has been used as noted earlier, but the disorder, while similar to multifocal conduction block, more resembles CIDP. The disease is not directly connected to antibodies against GMl, but a few patients with the sensorimotor disorder will display them. **Treatment** For multifocal motor conduction block and motor neuropathy, with or without anti-GM1 antibodies, **IVIg** infusions have been effective, albeit temporarily, in more than half of patients. Some authoritative clinicians favor the early **addition of rituximab** in treatment-resistant cases or when the frequency of infusions is unsustainable and if that fails, **cyclophosphamide**. Other immune-modulating drugs have been tried in small series with various results. There is ***no response to corticosteroids***. The **MADSAM illness responds similarly to corticosteroids, IVIg, or plasma exchange, similar to the effects of these approaches in CIDP.**

Answer 7

IVIG מדובר פה ב MMN (multifocal motor neuropathy) **Treatment** For multifocal motor conduction block and motor neuropathy, with or without anti-GM1 antibodies, **IVIg** infusions have been effective, albeit temporarily, in more than half of patients. Some authoritative clinicians favor the early **addition of rituximab** in treatment-resistant cases or when the frequency of infusions is unsustainable and if that fails, **cyclophosphamide**. Other immune-modulating drugs have been tried in small series with various results. There is ***no response to corticosteroids***. The **MADSAM illness responds similarly to corticosteroids, IVIg, or plasma exchange, similar to the effects of these approaches in CIDP.**

Answer 8

Anti GM-1 **Multifocal motor neuropathy**, is associated in half of cases with a **particular IgM antibody, anti-GMI** directed against a **ganglioside component of peripheral myelin** Multifocal motor neuropathy and motor conduction block **predominate in men**. They usually begin with an acute or subacute **motor mononeuropathy**, manifest, for example, as weakness of the wrist or foot-drop, and are often **joined insidiously by another** focal motor palsy. The **process is painless, unlike vasculitic mononeuritis multiplex,** involves the nerve incompletely, and, in its usual form, is **unaccompanied by any sensory symptoms** such as paresthesias or numbness. Despite the initially demyelinating character of the disorder, there is almost always **atrophy of the weakened muscle** within months and there may be a **few fasciculations**, thus simulating ALS. Nevertheless, the **weakness tends to be disproportionate to atrophy**. Usually, the **tendon reflex is lost or muted** in an affected region, but for unexplained reasons, some patients have one or more brisk reflexes. Our experience has been that this latter reflex change does not reach the point of appearing "pathologic" and that clonus and Babinski signs are categorically not part of the illness, as they are in ALS. **Treatment** For multifocal motor conduction block and motor neuropathy, with or without anti-GM1 antibodies, **IVIg** infusions have been effective, albeit temporarily, in more than half of patients. Some authoritative clinicians favor the early **addition of rituximab** in treatment-resistant cases or when the frequency of infusions is unsustainable and if that fails, **cyclophosphamide**. Other immune-modulating drugs have been tried in small series with various results. There is ***no response to corticosteroids***.

Answer 9

Anti GM1 -MMN איך לשלול מסיחים אחרים- Anti Yo – Cerebellar Syndrome Anti HU – Sensory, encephalitis ESR – GCA, PMR Anti GM1 – CIDP, MMN **Multifocal motor neuropathy**, is associated in half of cases with a **particular IgM antibody, anti-GMI** directed against a **ganglioside component of peripheral myelin** Multifocal motor neuropathy and motor conduction block **predominate in men**. They usually begin with an acute or subacute **motor mononeuropathy**, manifest, for example, as weakness of the wrist or foot-drop, and are often **joined insidiously by another** focal motor palsy. The **process is painless, unlike vasculitic mononeuritis multiplex,** involves the nerve incompletely, and, in its usual form, is **unaccompanied by any sensory symptoms** such as paresthesias or numbness. Despite the initially demyelinating character of the disorder, there is almost always **atrophy of the weakened muscle** within months and there may be a **few fasciculations**, thus simulating ALS. Nevertheless, the **weakness tends to be disproportionate to atrophy**. Usually, the **tendon reflex is lost or muted** in an affected region, but for unexplained reasons, some patients have one or more brisk reflexes. Our experience has been that this latter reflex change does not reach the point of appearing "pathologic" and that clonus and Babinski signs are categorically not part of the illness, as they are in ALS. **Treatment** For multifocal motor conduction block and motor neuropathy, with or without anti-GM1 antibodies, **IVIg** infusions have been effective, albeit temporarily, in more than half of patients. Some authoritative clinicians favor the early **addition of rituximab** in treatment-resistant cases or when the frequency of infusions is unsustainable and if that fails, **cyclophosphamide**. Other immune-modulating drugs have been tried in small series with various results. There is ***no response to corticosteroids***.

Answer 10

קמפילובקטר- הסיבה הויראלית השכיחה יותר לגיליאן ברה. *The defining feature was the presence of numerous electrically inexcitable motor nerves and signs of extensive denervation* WNV+ mycoplasma= myelitis- does not ascenf

Answer 11

anti GM1 or Anti GD1 * *Beyond the close association between autoantibodies to GQ 1b and Fisher syndrome or other variants that include ophthalmoplegia as mentioned previously other antiganglioside antibodies have become of interest in GBS. The **acute motor axonal variety has a tendency to be associated with antibodies to GM1 or GD1a** and the pharyngealcervicalbrachial syndrome, to GT1a.* * Approximately one fifth of patients have anti GM1 antibodies early in their course, corresponding in most instances to a predominantly motor presentation and to axonal damage, the highest titers being associated with cases that follow Campylobacter infections. Antibodies directed against GD1a or GT1b are associated in some cases with the pharyngeal-brachial-cervical variant. * anti MAG- sensory motor- associated with MGUS

Answer 12

150 תאים לבנים בניקור שולל גיליאן ברה

Answer 13

להשלים עוד שני ימי טיפול ב IVIG As effective as plasma exchange is, IVIg (0.4 g/kg per day for **5 consecutive days**) is easier to administer and probably safer than plasma exchange because there is no need for large intravenous access. The clinical improvement that follows the administration of IVIg or plasma exchange usually cannot be readily discerned in an individual patient; i.e., it is apparent only by comparing large groups of treated and untreated patients. For this reason it is not possible to judge that a patient who fails to improve or who worsens through the period of treatment has derived no benefit from therapy.

Answer 14

פעלות ספונטנית במנוחה בבדיקה אלקטרו-מיוגרפית מעיד על דה-נרווציה ונזק אקסונלי

Answer 15

הפגיעה הדיסאוטונומית בגיליאן ברה היא בבארורצפטורים וסיבים פוסט גנגליונים.

Answer 16

דה נרווציה בשרירים בגלל פגיעה אקסונלית

Answer 17

decreased CMAP= axonal= worse prognosis

Answer 18

plasmapheresis בגלל חסר ידוע ב- IgA

Answer 19

attachment of complement to myelin surface **Complement also seems to be a necessary factor in the initial attack on myelin.** complement-dependent myelin damage by **immunoglobulin (Ig) M antimyelin** antibodies in GBS provided evidence that antimyelin antibodies are able to initiate myelin destruction even through T cells and that macrophages are the ultimate effectors of the damage. Indeed, **the very earliest change that could be detected** by Hafer-Macko and colleagues was the **deposition of complement on the inner layer of myelin**.

Answer 20

היפותירואידיזם רק מתקדמת ללא התקפים אקוטים. חולפת לחלוטין לאחר טיפול ולעיתים אף רברסבילית. **Polyneuropathy With Hypothyroidism** Although *characteristic disturbances of skeletal muscle* are known to complicate hypothyroidism, the *demonstration of a definite polyneuropathy has been infrequent*. **Loss of reflexes, diminution in vibratory, joint-position, and touch-pressure sensations, and weakness in the distal parts of the limbs are the usual findings seldom severe**. Nerve conduction velocities are **slowed** and the **protein content of the CSF is usually increased to more than 100 mg/dL**. Possibly the latter finding is a reflection of the increased protein content of the serum in the hypothyroid state. **The subjective improvement and complete or near-complete reversibility of neuropathic signs following treatment with thyroid hormones provides evidence of a hypothyroid etiology.** In biopsies of nerve, an **edematous protein infiltration of the endoneurium and perineurium**, a kind of metachromatic mucoid material, has been seen. noted segmental demyelination in teased fiber preparations. In electron-microscopic sections, a slight increase in glycogen, acid mucopolysaccharides, and aggregates of glycogen and cytoplasmic laminar bodies in Schwann cells have been observed by others. Polyneuropathy of sensorimotor type has also been observed in association with a syndrome of chronic lymphocytic thyroiditis and alopecia (Hart et al). מסיחים אחרים- **Refsum**: * AR – **may have relapsing course** * S&S: Eyes: RP, pupil abnormality, nyctalopsia Ears: deafness Heart : cardiomyopathy Skin: Ichthyosis Neuro: 1. ataxia, 2. chronic polyneuropathy – sensorimotor, legs>arms, deep>pain 3. Anosmia 4. Onion bulb * Ix: CSF – protein increased Serum - Increased Phytanic Acid * Rx: low phytol **Porphyria**: * **Acute intermittent** * AD * Metabolic defect in liver – increased production and urinary Excretion of **porphobilinogen and delta-aminolevulinic acid**. * **Severe rapid advancing mainly motor polyneuropathy** – Commonly **bibrachial weakness and truncal sensory loss** Tachycardia Abdominal pain Psychosis Convulsions * **Exacerbated by drugs**: sulfonamides, estrogens, barbiturates, phenytoin * CSF – protein normal or elevated * RX: IV glucose and hematin ## Footnote **Polyneuropathy with hypothyroidism** * Distal sensorimotor * Seldom severe * CSF protein increased * Complete reversibililty with hormone treatment

Answer 21

היפותירואידיזם רק מתקדמת ללא התקפים אקוטים. חולפת לחלוטין לאחר טיפול ולעיתים אף רברסבילית. **Polyneuropathy With Hypothyroidism** Although *characteristic disturbances of skeletal muscle* are known to complicate hypothyroidism, the *demonstration of a definite polyneuropathy has been infrequent*. **Loss of reflexes, diminution in vibratory, joint-position, and touch-pressure sensations, and weakness in the distal parts of the limbs are the usual findings seldom severe**. Nerve conduction velocities are **slowed** and the **protein content of the CSF is usually increased to more than 100 mg/dL**. Possibly the latter finding is a reflection of the increased protein content of the serum in the hypothyroid state. **The subjective improvement and complete or near-complete reversibility of neuropathic signs following treatment with thyroid hormones provides evidence of a hypothyroid etiology.** In biopsies of nerve, an **edematous protein infiltration of the endoneurium and perineurium**, a kind of metachromatic mucoid material, has been seen. noted segmental demyelination in teased fiber preparations. In electron-microscopic sections, a slight increase in glycogen, acid mucopolysaccharides, and aggregates of glycogen and cytoplasmic laminar bodies in Schwann cells have been observed by others. Polyneuropathy of sensorimotor type has also been observed in association with a syndrome of chronic lymphocytic thyroiditis and alopecia (Hart et al). מסיחים אחרים- **Refsum**: * AR – **may have relapsing course** * S&S: Eyes: RP, pupil abnormality, nyctalopsia Ears: deafness Heart : cardiomyopathy Skin: Ichthyosis Neuro: 1. ataxia, 2. chronic polyneuropathy – sensorimotor, legs>arms, deep>pain 3. Anosmia 4. Onion bulb * Ix: CSF – protein increased Serum - Increased Phytanic Acid * Rx: low phytol **Porphyria**: * **Acute intermittent** * AD * Metabolic defect in liver – increased production and urinary Excretion of **porphobilinogen and delta-aminolevulinic acid**. * **Severe rapid advancing mainly motor polyneuropathy** – Commonly **bibrachial weakness and truncal sensory loss** Tachycardia Abdominal pain Psychosis Convulsions * **Exacerbated by drugs**: sulfonamides, estrogens, barbiturates, phenytoin * CSF – protein normal or elevated * RX: IV glucose and hematin ## Footnote **Polyneuropathy with hypothyroidism** * Distal sensorimotor * Seldom severe * CSF protein increased * Complete reversibililty with hormone treatment

Answer 22

סימני דה-נרבציה מפושטת **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 23

סימני דה-נרבציה מפושטת **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 24

השאלה מכוונת לצלע צווארית כחלק מה thoracic outlet syndrome עם זאת גם פגיעת פנקוסט יכולה לגרום ללחץ על המדיאל קורד של הברכיאל פלקסוס. (אני חושבת שאם היו מכוונים לשם היו נותנים לנו גם תמונה של הורנר) A primarily neurologic problem may characterize the thoracic outlet syndrome. There is slight wasting and weakness of the hypothenar, interosseous, adductor pollicis, and deep flexor muscles of the fourth and fifth fingers (i.e., the **muscles innervated by the lower trunk of the brachial plexus and ulnar nerve**). Weakness of the flexor muscles of the forearm may be present in advanced cases. Tendon reflexes are usually preserved. In addition, most patients complain of an intermittent aching of the arm, particularly of the ulnar side, and about half of them complain also of numbness and tingling along the ulnar border of the forearm and hand. A loss of superficial sensation in these areas is variable. It may be possible to reproduce the sensory symptoms by firm pressure just above the clavicle or by traction on the arm. Vascular features are often absent or minimal in patients with the neurologic form of the syndrome. * Two important nerves emerge from the upper trunk (dorsal scapular nerve to the rhomboid and levator scapulae muscles, and long thoracic nerve to the anterior serratus). The posterior cord gives rise mainly to the radial nerve. The medial cord gives rise to the ulnar nerve, medial cutaneous nerve to the forearm, and medial cutaneous nerve to the upper arm. This cord lies in close relation to the subclavian artery and apex of the lung and is the part of the plexus most susceptible to traction injuries and to compression by tumors that invade the costoclavicular space. The median nerve is formed by the union of parts of the medial and lateral cords.

Answer 25

ג. חולשה של התחלת האבדוקציה של הזרוע The **fifth cervical root syndrome**, produced by disc herniation between the fourth and fifth vertebral bodies, is characterized by **pain in the shoulder and trapezius region and by supra- and infraspinatus weakness**, manifest by an ***inability to abduct the arm* and rotate it externally with the shoulder adducted** (weakness of the supra- and infraspinatus muscles). There may be a **slight degree of weakness of the biceps and a corresponding reduction in the reflex**, but these are inconsistent findings. A small patch of diminished sensation commonly overlies the deltoid muscle.

Answer 26

**Posterior interosseous nerve** the radial nerve continues below the elbow as the posterior interosseous nerve, which innervates the **extensor muscles of the wrist and fingers, the main abductor of the thumb** (the abductor pollicis longus, which is easier to isolate than the median nerve innervated abductor pollicis brevis), and the **extensors of the fingers at both joints**. If the lesion is confined to the posterior interosseous nerve, **only the extensors of the wrist and fingers are affected**

Answer 27

sciatic nerve **Sciatic Nerve** * Origin L4, L5, S1, S2 * Supplies **motor innervation to hamstring** muscles And **muscles below the knee** via: The **Tibial Nerve** and the **Peroneal Nerve**. * Conveys **sensory information from *posterior* aspect of thigh** **Posterior and lateral aspects of *leg and the entire sole** * **complete sciatic paralysis** – **knee cannot be flexed**, **all muscles below knee paralysed**. Weakness of gluteal muscles and pain in the buttock and posterior thigh point to nerve involvement in the pelvis. * If beyond the sciatic notch – sparing of gluteal muscles but not hamstrings * mostly partial compresisve lesions – **peroneal > tibial**. * **Patterns of involvement**: 1. L4-L5 disc compressing **L5 root**: **pain in *posterolateral thigh and leg*** with **numbness over the inner foot** and **weakness of dorsiflexion** of the foot and toes; 2. LS-Sl disc compressing **Sl root**: **pain in posterior thigh and leg**, **numbness of lateral foot**, weakness of **foot plantar flexion and loss of ankle jerk**.

Answer 28

Anterior interosseous nerve (המשכי למדיאן נרב) שלילת המסיחים האחרים: -medial cord: combined Median and Ulnar and proximal weakness - Ulnar Nerve: 4-5th phalanges, Inter Ossei - Musculocutaneous nerve – Biceps - Posterior Interosseous Nerve – distal end of radial nerve

Answer 29

עצב פרונאלי **Common Peroneal (Fibular) Nerve** Just above the popliteal fossa the sciatic nerve divides into the tibial nerve (medial, or internal, popliteal nerve) and the **common peroneal nerve** (lateral, or external, popliteal nerve). The latter swings around the head of the fibula to the anterior aspect of the leg, giving off the * **superficial peroneal nerve** that provides **musculocutaneous branches** (to the peroneal muscles) and to the * **deep peroneal nerve** (formerly called anterior tibial nerve) supplies the **dorsiflexors of the foot and toes** (anterior tibialis, extensor digitorum longus and brevis, and extensor hallucis longus muscles) and carry **sensory fibers from the dorsum of the foot and lateral aspect of the lower half of the leg**. * There was weakness of dorsiflexion of the foot (footdrop) and **Weakness of eversion** of the foot is usually demonstrable; because *inversion is a function of the L5 root and the tibial nerve, it is spared in peroneal palsy*, thereby allowing a distinction between footdrop at the two sites. (Foot eversion should be tested with the ankle passively dorsiflexed.) Pain is variable. * Pressure during an operation or sleep or from tight plaster casts, obstetric stirrups, habitual and prolonged crossing of the legs while seated, and tight knee boots are the most frequent causes of injury to the common peroneal nerve. The **point of compression of the nerve is where it passes over the head of the fibula**. Emaciation in patients with cancer or AIDS increases the incidence of these types of compressive injuries. The nerve may also be affected in diabetic neuropathy and injured by fractures of the upper end of the fibula. A Baker cyst, which consists of inflamed synovium extending into the retropopliteal space, may compress the nerve, and it may be damaged by muscle swelling or small hematomas behind the knee in asthenic athletes. * The prognosis is generally good in cases of partial paralysis.

Answer 30

Abductor pollicis longus The radial nerve may be compressed in the axilla (“crutch” palsy), but more frequently at a lower point, where the nerve winds around the humerus pressure palsies incurred during an alcoholic stupor and fractures of the humerus commonly injure the nerve at the site of injury. It is susceptible to lead intoxication and is frequently involved as part of brachial neuritis and mononeuritis multiplex.

Answer 31

Tibialis posterior **Patterns of involvement**: 1. L4-L5 disc compressing **L5 root**: **pain in *posterolateral thigh and leg*** with **numbness over the inner foot** and **weakness of dorsiflexion** of the foot and toes; 2. LS-Sl disc compressing **Sl root**: **pain in posterior thigh and leg**, **numbness of lateral foot**, weakness of **foot plantar flexion and loss of ankle jerk**. **Lesions of the fifth lumbar root (L5)** produce **pain in the region of the hip and posterolateral thigh** (i.e., sciatica) and, in more than half such cases, **lateral calf** (to the lateral malleolus), and less often, the **dorsal surface of the foot and the first or second and third toes**. Pain is elicited by the **straight-leg raising test** or one of its variants, and protective nocifensive reflexes come into play, limiting further elevation of the leg. Paresthesia may be felt in the entire territory or only in its distal parts. The **tenderness is in the lateral gluteal region and near the head of the femur.** **Weakness**, if present, involves the **extensors of the big toe and foot and the foot invertors** (a distinguishing feature of foot drop originating from peroneal nerve damage, which spares inversion because it is a tibial nerve function). The **ankle jerk may be diminished** (more often it is normal), but the knee jerk is hardly ever altered.

Answer 32

inferior gluteal

Answer 33

בדם הפריפרי אאוזינופיליה בולטת- **Polyarteritis Nodosa** Almost 75 percent of cases of polyarteritis nodosa include involvement of the **small nutrient arteries of peripheral nerves**, symptomatic form of neuropathy develops in about half this number. involvement of the peripheral nerves may be the principal or first sign of the disorder, before the main systemic **components of the clinical picture—abdominal pain, hematuria, fever, *eosinophilia*, hypertension, vague limb pains, and asthma**. Although characteristically a disease of **multiple discrete mononeuropathies**, the syndrome associated with polyarteritis nodosa **may appear more or less generalized and symmetrical as a result of the accumulation of many *small nerve infarctions***; elements of mononeuritis that have been engrafted on an otherwise generalized process. For example, an ***asymmetrical foot- or wrist-drop* or a disproportionate affection of one nerve in a limb**, such as ulnar palsy with relative sparing of function of the adjacent median nerve, are clues to the **multifocal nature** of the process. As often it takes form of random infarctions of two or more individual nerves. The **onset is usually abrupt with symptoms of pain or numbness at a focal site along a nerve or in the distal distribution of an affected nerve, followed in hours or days by motor or sensory loss in the distribution of that nerve and then by involvement in a saltatory fashion of other peripheral nerves**. Both the spinal and cranial nerves may be affected but far less often than the nerves in the limbs. The **CSF is usually normal**. **Nerve biopsy**, from the sural nerve, show the **necrotizing arteritis in medium-size vessels** (fibrinoid necrosis of all 3 coats of the vessel walls), with **infiltrating *eosinophils*** and occlusion of vessels. Muscle biopsy may also show perivascular inflammation and necrosis, On the basis of the smaller size of affected vessels and the presence of perinuclear antinuclear cytoplasmic autoantibodies **(p-ANCA)**, It has been designated as a “microscopic” polyarteritis. **Rapidly progressive glomerulonephritis and lung hemorrhage** are the additional features of the latter disease, neuropathy occurring somewhat less frequently than in typical polyarteritis. **Treatment** Based on the response to the systemic vasculitides with ANCA activity, mononeuritis multiplex caused by vasculitis has been treated with **corticosteroids** and either **rituximab** 375 mg/m2 weekly for 4 weeks, or **cyclophosphamide** 1 g/m2 intravenously once a month for several months, *corticosteroids alone are often inadequate*, **Azathioprine** is a reasonable alternative if cyclophosphamide is not tolerated. Treatment usually must be **continued for at least several months**. In intractable cases and in those with systemic involvement, **treatment with methotrexate may be indicated**, or this may be used initially. Spontaneous remission and therapeutic arrest are known, but many cases have a fatal outcome from kidney and systemic complications. **The infarctive nerve palsies and sensory loss of the mononeuropathies generally persist to a large degree even when the systemic disease is brought under control.**

Answer 34

גלומרולונפריטיס **Polyarteritis Nodosa** Almost 75 percent of cases of polyarteritis nodosa include involvement of the **small nutrient arteries of peripheral nerves**, symptomatic form of neuropathy develops in about half this number. involvement of the peripheral nerves may be the principal or first sign of the disorder, before the main systemic **components of the clinical picture—abdominal pain, hematuria, fever, *eosinophilia*, hypertension, vague limb pains, and asthma**. Although characteristically a disease of **multiple discrete mononeuropathies**, the syndrome associated with polyarteritis nodosa **may appear more or less generalized and symmetrical as a result of the accumulation of many *small nerve infarctions***; elements of mononeuritis that have been engrafted on an otherwise generalized process. For example, an ***asymmetrical foot- or wrist-drop* or a disproportionate affection of one nerve in a limb**, such as ulnar palsy with relative sparing of function of the adjacent median nerve, are clues to the **multifocal nature** of the process. As often it takes form of random infarctions of two or more individual nerves. The **onset is usually abrupt with symptoms of pain or numbness at a focal site along a nerve or in the distal distribution of an affected nerve, followed in hours or days by motor or sensory loss in the distribution of that nerve and then by involvement in a saltatory fashion of other peripheral nerves**. Both the spinal and cranial nerves may be affected but far less often than the nerves in the limbs. The **CSF is usually normal**. **Nerve biopsy**, from the sural nerve, show the **necrotizing arteritis in medium-size vessels** (fibrinoid necrosis of all 3 coats of the vessel walls), with **infiltrating *eosinophils*** and occlusion of vessels. Muscle biopsy may also show perivascular inflammation and necrosis, On the basis of the smaller size of affected vessels and the presence of perinuclear antinuclear cytoplasmic autoantibodies **(p-ANCA)**, It has been designated as a “microscopic” polyarteritis. ***Rapidly progressive glomerulonephritis and lung hemorrhage*** are the additional features of the latter disease, neuropathy occurring somewhat less frequently than in typical polyarteritis. **Treatment** Based on the response to the systemic vasculitides with ANCA activity, mononeuritis multiplex caused by vasculitis has been treated with **corticosteroids** and either **rituximab** 375 mg/m2 weekly for 4 weeks, or **cyclophosphamide** 1 g/m2 intravenously once a month for several months, *corticosteroids alone are often inadequate*, **Azathioprine** is a reasonable alternative if cyclophosphamide is not tolerated. Treatment usually must be **continued for at least several months**. In intractable cases and in those with systemic involvement, **treatment with methotrexate may be indicated**, or this may be used initially. Spontaneous remission and therapeutic arrest are known, but many cases have a fatal outcome from kidney and systemic complications. **The infarctive nerve palsies and sensory loss of the mononeuropathies generally persist to a large degree even when the systemic disease is brought under control.** * Chrug Strauss: Eosinophils Involves the lung and skin -rhinitis and asthma Neuropathy – commonly presents As acute, painful, mononeuritis multiplex C-ANCA Eosinophilic infiltration more pronounced than PAN

Answer 35

1. Polyarteritis nodosa **Polyarteritis Nodosa** Almost 75 percent of cases of polyarteritis nodosa include involvement of the **small nutrient arteries of peripheral nerves**, symptomatic form of neuropathy develops in about half this number. involvement of the peripheral nerves may be the principal or first sign of the disorder, before the main systemic **components of the clinical picture—abdominal pain, hematuria, fever, *eosinophilia*, hypertension, vague limb pains, and asthma**. Although characteristically a disease of **multiple discrete mononeuropathies**, the syndrome associated with polyarteritis nodosa **may appear more or less generalized and symmetrical as a result of the accumulation of many *small nerve infarctions***; elements of mononeuritis that have been engrafted on an otherwise generalized process. For example, an ***asymmetrical foot- or wrist-drop* or a disproportionate affection of one nerve in a limb**, such as ulnar palsy with relative sparing of function of the adjacent median nerve, are clues to the **multifocal nature** of the process. As often it takes form of random infarctions of two or more individual nerves. The **onset is usually abrupt with symptoms of pain or numbness at a focal site along a nerve or in the distal distribution of an affected nerve, followed in hours or days by motor or sensory loss in the distribution of that nerve and then by involvement in a saltatory fashion of other peripheral nerves**. Both the spinal and cranial nerves may be affected but far less often than the nerves in the limbs. The **CSF is usually normal**. **Nerve biopsy**, from the sural nerve, show the **necrotizing arteritis in medium-size vessels** (fibrinoid necrosis of all 3 coats of the vessel walls), with **infiltrating *eosinophils*** and occlusion of vessels. Muscle biopsy may also show perivascular inflammation and necrosis, On the basis of the smaller size of affected vessels and the presence of perinuclear antinuclear cytoplasmic autoantibodies **(p-ANCA)**, It has been designated as a “microscopic” polyarteritis. ***Rapidly progressive glomerulonephritis and lung hemorrhage*** are the additional features of the latter disease, neuropathy occurring somewhat less frequently than in typical polyarteritis. **Treatment** Based on the response to the systemic vasculitides with ANCA activity, mononeuritis multiplex caused by vasculitis has been treated with **corticosteroids** and either **rituximab** 375 mg/m2 weekly for 4 weeks, or **cyclophosphamide** 1 g/m2 intravenously once a month for several months, *corticosteroids alone are often inadequate*, **Azathioprine** is a reasonable alternative if cyclophosphamide is not tolerated. Treatment usually must be **continued for at least several months**. In intractable cases and in those with systemic involvement, **treatment with methotrexate may be indicated**, or this may be used initially. Spontaneous remission and therapeutic arrest are known, but many cases have a fatal outcome from kidney and systemic complications. **The infarctive nerve palsies and sensory loss of the mononeuropathies generally persist to a large degree even when the systemic disease is brought under control.** על המסיחים האחרים * **Diphteric**- עצבים קרניאליים ,בולבארי הפרעה באקומודציה טישטוטש ראייה מתחיל שבוע אחרי * **Porhyric** :A **severe, rapidly advancing, more or less symmetrical and mainly motor polyneuropathy**—often with abdominal pain, psychosis (delirium or confusion), or convulsions— may be a manifestation of acute intermittent porphyria. disease can be identified after some time by its characteristic recurrent attacks, often precipitated by drugs such as sulfonamides, griseofulvin, estrogens.

Answer 36

**Primary systemic amyloidosis** **Acquired Primary (Nonfamilial, AL) Amyloid Neuropathy** numerous sporadic instances of a **peripheral neuropathy caused by amyloid deposition**. As in the familial variety, the **heart, kidneys, and gastrointestinal tract may be involved**. also been called **primary systemic amyloidosis.** only 26 percent of patients with primary amyloidosis had a malignant plasma cell dyscrasia. ‘other series have found rates of myeloma as high as 75 percent. In any case, **90 percent of primary amyloidosis is the result of a monoclonal protein in the blood (rarely polyclonal)**. Macrophage enzymes cleave the larger immunoglobulin molecules and the **light chains aggregate to form amyloid deposits in tissue, or the plasma cells may produce light chains directly (“light chain disease”)**. ***Lambda light chain predominates in the idiopathic variety of amyloidosis and kappa light chain is more common in myeloma***. In a few cases, the light chain is found only in the urine (as Bence Jones protein). * Secondary amyloidosis (AA), the result of chronic infection or other chronic disease outside the nervous system and, as a rule, is *not associated with neuropathy* * familial amyloidosis, a third variety, is *almost invariably associated with neuropathy but is associated with a paraprotein in only a small proportion of cases and the amount of immunoglobulin is small* **Primary amyloidosis** is mainly a disease of **older men**, the median age at the time of diagnosis being **65 years**. The neuropathic symptoms and signs are similar to those of hereditary amyloid polyneuropathy, but the progress of the disease is considerably **more rapid**. The **initial syndrome is primarily sensory**—numbness, paresthesias, and very often, acral pain—signs that are mainly characteristic of involvement of **small-diameter sensory fibers (loss of pain and thermal sensation)**. It is the **painful aspect and the autonomic features** discussed later that distinguish this disease from the other paraproteinemic neuropathies. **Weakness follows**, initially limited to the feet but becoming more extensive as the disease progresses and eventually **spreads** to the hands and arms. Only **later is there loss of mainly large fibers that mediate sensations of touch, pressure, and proprioception**. Twenty-five percent of patients have carpal tunnel syndrome from infiltration of the flexor retinaculum. **Autonomic involvement can be severe in amyloid neuropathy (familial or primary)** and may become **evident early in the course of the illness**; disturbances of **gastrointestinal motility such as episodic diarrhea and orthostatic dizziness or erectile dysfunction and bladder disturbances**. The pupils may show a *slow reaction to light*, or there may be a reduction in sweating. An infiltrative amyloid myopathy also occurs as a rare complication of the disease; it presents as an enlargement and induration of many muscles, particularly those of the tongue (macroglossia), pharynx, and larynx

Answer 37

5. כל התשובות נכונות | הטבלה לא נמצאת במהדורה האחרונה של אדאמס אבל היא טובה

Answer 38

sarcoid * CSF in Sarcoid: A slight **lymphocytic pleocytosis** (10 to 200 cells/mm3) and a **moderate increase in protein content** (generally without oligoclonal bands), consistent with meningeal involvement are the usual CSF findings but many cases show no change. קצת על המסיחים האחרים 1. **Behcet**: * **Chronic recurrent vasculitis** – involving small vessels * m>f * Originally triad of: **relapsing iridocyclitis, recurrent oral and genital ulcers** * **Systemic features**: erythema nodosum, thrombophlebitis, polyarthritis, UC. * **Diagnostic criteria**: recurrent apthous or herpetiform oral ulceration, recurrent genital ulceration, anterior or posterior uveitis, cells in vitreous or retinal vasculitis, erythema nodosum. * 30% CNS involvement * **CNS manifestations**: **Meningoencephalitis, CN palsies** (6ht most common), cerebellar **ataxia**, **corticospinal** tract signs, venous occlusion. * **CSF** – pleocytosis, protein elevated, glucose normal * CNS clears , but may recur * Treat with steroids. 2. **Lyme: Burrelia Burgdorferi** * **Acute radicular pain**, followed by chronic **lymphocytic meningitis** and frequently accompanied by peripheral and cranial **neuropathies**. * In USA - initial manifestation erythema migrans, fatigue, myalgia, arthralgia, headache. * European variant – painful lymphocytic meningoradiculitis. Bannwarth syndrome * **CNS** – aseptic meningitis or fluctuating meningoencephalitis with CN or peripheral nerve involvement lasting months * **Caridac involvement** – myocarditis, pericarditis, AV block. * **CSF** – count 50-3000, protein levels 75-400,glucose NAD. * **ELISA** – IgM response followed by IgG. PCR * **Doxycycline** if early treatment, later - **Ceftriaxone** 3. **leptomeningeal metastases** (carcinomatous meningitis), neoplastic cells extend throughout the leptomeninges and involve cranial and spinal nerve roots, producing a picture of **meningoradiculitis with normal or low CSF glucose values**.

Answer 39

סרקואיד The **essential lesion in sarcoidosis** consists of focal collections of **epithelioid cells surrounded by a rim of Lymphocytes**; frequently there are ***giant cells***, but **caseation is lacking**. The sarcoid, **noncaseating granuloma may be found in all organs and tissues**, including the nerve roots, peripheral, and central nervous systems, but the most frequently involved are the mediastinal and peripheral lymph nodes, lungs, liver, skin, phalangeal bones, eyes, and parotid glands. * isolated sarcoid granulomas **may involve peripheral or cranial nerves, subacute or chronic polyradiculopathy, neuropathy, or plexopathy of asymmetrical type**. * Polyneuropathy may occur, but is infrequent * Of the cranial nerves, the **facial is the most frequently involved The facial palsy may be unilateral or bilateral**. * **Blindness, uveitis and optic neuropathy**. * **Myopathy** * In the CNS, sarcoidosis takes the form of a **granulomatous infiltration of the meninges and underlying Parenchyma**, most frequent at the base of the circumscribed lesion of the stalk of the **pituitary gland, optic chiasm, and hypothalamus**, it causes **visual disturbances, polydipsia, polyuria, or somnolence**. * **Hydrocephalus, seizures, palsies, and corticospinal and cerebellar signs are other occasional manifestations**. * Rarely, sarcoid can be a cause of a **chronic recurrent or persistent meningitis, or severe, steroid-responsive headache.** * Granulomas may present as a mass or as one or more focal infiltrating cortical and subcortical lesions that tend to follow the course of superficial cortical veins. * cerebral signs, including **seizures**, presumably caused by deposits of sarcoid in the brain, are observed but are uncommon. Among the odd focal syndromes reported are an **amnestic or dementing condition from infiltration of the medial temporal lobes and psychotic and related behavioral aberrations**. In addition to this leptomeningitis, there is an infiltration of the **dura, a pachymeningitis**. * The **spinal meninges and spinal cord** may be infiltrated, usually independently of brain involvement, imparting a picture of **chronic adhesive arachnoiditis or an inflammatory Myelopathy**. There is more prominent focal contrast enhancement and T2 signal abnormality on MRl than is usual for a demyelinating disease. It is one of the causes of a **"longitudinally extensive myelopathy“**. * **Diagnosis** A **slight lymphocytic pleocytosis (10 to 200 cells/mm3) and a moderate increase in protein content (generally without oligoclonal bands**), consistent with meningeal involvement are the usual CSF findings but many cases show no change. The **glucose content is normal or slightly reduced**. The spinal form may be associated with **CSF block and a resultant greatly raised protein content**. The diagnosis of **neurosarcoidosis** is made on the basis of the **clinical features together with clinical and biopsy evidence of sarcoid granulomas** in other tissues (lymph nodes, lungs, bones, uvea, skin, and muscle). The history or presence of **erythema nodosum or iritis** further raises suspicion of this process. If a conventional chest radiograph does not disclose the **characteristic bilateral hilar adenopathy of sarcoidosis**, a thoracic CT scan may be obtained. In patients in whom the clinical suspicion remains high, positron emission tomography (**PET**) scanning may be useful to identify inflamed lymph nodes that are amenable to biopsy. The contrast-enhanced CT or MRI are useful means of detecting meningeal involvement and MRI may disclose **periventricular and white matter lesions**, although the latter pattern is usually not at all specific.

Answer 40

סרקואידוזיס. כשבלוטת הפרוטיד גדולה ויש שיתוק אקוטי של שרירי הפנים דו"צ זה נקרא- HERFORD SYNDROME =UVEOPAROTID SYNDROME

Answer 41

נוכחות של conduction block תשלול hereditary sensory and autonomic neuropathy **Mutilating Hereditary (Dominant) Sensory Polyneuropathy in Adults (Hereditary Sensory and Autonomic Neuropathy Type 1)** The **characteristic** features of this group of polyneuropathies are an **autosomal dominant** mode of inheritance and onset of symptoms in the **second decade** or later. Characteristically this begins with **subtle loss of sensation for painful stimuli in the feet** (e.g., inability to feel the hot sand or hot water in a tub). As the disease evolves, there is involvement of the feet with **calluses of the soles** and, later, episodes of **blistering**, **ulceration**, and **lymphangitis** followed by **osteomyelitis** and **osteolysis**, **shooting pains, distal sensory loss with *greater affection of pain and thermal sensation* than of touch and pressure, loss of sweating, diminution or absence of tendon reflexes, and *only slight loss of muscle power***. Over time, loss of pain sensation in the fingers leads to **fingertip ulcerations**, osteomyelitis, and amputations. Some patients have a **mild pes cavus** and **weakness of the peroneal and pretibial muscles, with foot-drop and steppage gait**. **Lancinating pain**s may occur in the legs, thighs, and shoulders, and, exceptionally, the pain **may last for days or longer** and be as **disabling** as that of tabes dorsalis; however, **in the majority of patients there is no pain whatsoever**. **Neural deafness** was present in one of Denny-Brown's patients. In that case, which was studied postmortem, there was a *loss of small nerve cells in the lumbosacral dorsal root ganglia*; the *dorsal roots were thin*, and the *fibers* in the posterior columns of the spinal cord and those in the peripheral nerves were *diminished in number*. **Myelinated and unmyelinated fibers were both affected**. Both **axonal degeneration and segmental demyelination** have been demonstrated in teased nerve preparations. **Sensory nerve conduction may be absent or is *uniformly slowed* in every nerve tested.** It must be emphasized that despite its categorization as a "sensory and autonomic neuropathy;" the most common, dominantly inherited form, termed **HSAN1**, also entails **progressive, disabling, distal motor weakness**, a consequence of ongoing axonopathy and denervation. HSAN1 is a consequence of a loss of function of the **enzyme serine palmitoyltransferase**, which is the rate limiting step in the biosynthesis of **sphingolipids**.

Answer 42

True Focal and segmental **myokymias** differ in small ways from the generalized form of myokymia with regard to the timing and duration of the discharges. **The focal types refer mainly to facial myokymia**, seen most often in **multiple sclerosis, Guillain-Barre syndrome, large cerebellopontine angle tumors, or compression of the facial nerve** by a small aberrant blood vessel, but it may follow any peripheral nerve injury and regeneration. The **EMG** patterns are complex, either **high-frequency (30- to 100-Hz) recurrent bursts** or **brief lower-frequency Bursts**. **Segmental myokymia is a *common occurrence in demyelination and in radiation injuries of the brachial plexus***. The EMG **bursts tend to be longer and less frequent** than in generalized myokymia, and the interburst frequency is highly variable. The **origin** of these discharges is probably in the **distal peripheral nerve**, where activity of afferent fibers, possibly via ephaptic transmission, irregularly excites distal motor terminals. **Segmental myokymia** refers to **similar activity in the distribution of one or more adjacent motor roots** again, usually related in some way to demyelination. This activity **persists during sleep and general anesthesia**. * ***Fasciculations and myokymia are more likely to be seen in patients with radiation plexopathy, which seemingly occurs more frequently in patients with diabetic neuropathy**.

Answer 43

**porphobilinogen** and porphyrin precursor **Δ-aminolevulinic acid** **Porphyric Polyneuropathy** A **severe, rapidly advancing**, more or less **symmetrical** and **mainly motor polyneuropathy**—often with **abdominal pain, psychosis (delirium or confusion), or convulsions**— may be a manifestation of **acute *intermittent* porphyria**. **autosomal dominant trait** and is not associated with cutaneous sensitivity to sunlight. **The metabolic defect is in the liver and is marked by increased production and urinary excretion of porphobilinogen and of the porphyrin precursor Δ-aminolevulinic acid.** The peripheral and central nervous systems may also be affected in another hepatic type of porphyria (the variegate type). In the latter, the *skin is markedly sensitive to light and trauma*, and porphyrins are at all times found in the stools. Both of these hepatic forms of porphyria must be distinguished from the rarer *erythropoietic (congenital photosensitive) porphyria*, in which the *nervous system is not affected.* The **initial and often the most prominent symptom is *moderate to severe colicky abdominal pain***. Constipation and intestinal distention (ileus) are frequent. Attacks last for **days to weeks** and repeated vomiting may lead to inanition. *often precipitated by drugs such as **sulfonamides, griseofulvin, estrogens**, **Treatment** The use of **intravenous glucose and intravenous hematin** (4 mg/kg daily for 3 to 14 days) is recommended as the most effective therapy. Other aspects of treatment include respiratory support, use of beta-blocking agents (labetalol) if tachycardia and hypertension are severe, continued intravenous glucose to suppress the heme biosynthetic pathway, and *pyridoxine* (100 mg bid) on the supposition that vitamin B6 depletion has occurred

Answer 44

פורפיריה לא גורמת להגדלת עצבים פריפרים

Answer 45

חשיפת שתן לאור- פורפיריה נקודות מפתח – כאבי בטן ,פסיכוזה ,החמרה על פניטואין ,חולשה מתקדמת אבחנה- הימצאות פורפובילינוגן וחומצה אמינולובוליניק בשתן, כמו כן השתן נהיה שחור עקב חמצון הפורפובילינוגן.

Answer 46

אנזים תחליפי מדובר בפברי **Fabry** : * X linked recessive, * **Alpha-Galactosidase**, * accummulation of **Ceramide in endothelial, smooth muscle** of blood vessels , **renal** tubular, viscera and nerve cells. * Clinical: **lancinating pains** worse in **hot weather**, fever, exercise. **Diffuse vascular involvement**: HTN, renal damage, cardiomegaly, MI – thrombotic infarctions. characteristic **angiokeratomas**. * Rx – **enzyme replacement**

Answer 47

alpha galactosidase- Fabry **Fabry** : * X linked recessive, * **Alpha-Galactosidase**, * accummulation of **Ceramide in endothelial, smooth muscle** of blood vessels , **renal** tubular, viscera and nerve cells. * Clinical: **lancinating pains** worse in **hot weather**, fever, exercise. **Diffuse vascular involvement**: HTN, renal damage, cardiomegaly, MI – thrombotic infarctions. characteristic **angiokeratomas**. * Rx – **enzyme replacement** קצת על המסיח האחר- מחלת גושה 1)**Gaucher** * AR disease * Infantile presentation- Occulumotor apraxia , bilateral strabismus, rapid developmental delay. * Increase in **serum acid phosphatase** and characteristic histiocytes (**Gaucher Cells**) in biopsy. * **Deficiency of glucocerebrosidase** in leukocytes and hepatocytes is diganostic * Gaucher Cells – wrinkled appearance of cytoplasm and eccentricity of nucleus – accummulate in marrow, lungs, other viscera * Loss of neurons * Highyl diagnostic – **defect in voluntary gaze with normal doll’s eyes maneuver**. (in Nieman Pick – vertical eye movements lost) . 2) **Late Infantile and Early Childhood Gaucher Disease** As stated earlier, Gaucher disease usually develops in early infancy, but some cases, so-called Gaucher disease type Ill, may begin in **childhood, between 3 and 8 years** of age. The clinical picture is variable and combines features of infantile Gaucher disease-such as **abducens palsies, dysphagia, trismus, rigidity of the limbs, and dementia** with features of the late childhood-€arly adult form, such as **palsies of horizontal gaze, diffuse myoclonus, generalized seizures, and a chronic course**. The diagnosis is established by the finding of **splenomegaly, Gaucher cells, glucocerebroside storage, and deficient activity of glucocerebrosidase in leukocytes or cultured fibroblasts.** 3) **Late Gaucher Disease With Polymyoclonus** A type of Gaucher disease is occasionally encountered in which **seizures, severe diffuse myoclonus, supranuclear gaze disorders** (slow saccades, saccadic and pursuit horizontal gaze palsies), and **cerebellar ataxia** begin in **late childhood, adolescence, or adult life**. The course is **slowly Progressive**. The **intellect is relatively spared**. The **spleen is enlarged**. The pathologic and biochemical abnormalities are the same as those of Gaucher disease of earlier onset.

Answer 48

**Long thoracic nerve** This nerve is derived from the **fifth, sixth, and seventh cervical nerves** and supplies the **serratus anterior muscle**, which fixates the lateral scapula to the chest wall. Paralysis of this muscle results in an **inability to raise the arm over the head and winging of the *medial border* of the scapula** when the **outstretched arm is pushed forward against resistance**. The nerve is injured most commonly by **carrying heavy weights on the shoulder** or by strapping the shoulder to the operating table. קצת על המסיח השני- **Suprascapular Nerve** This nerve is derived from the **fifth (mainly) and sixth** cervical nerves and supplies the **supraspinatus and infraspinatus** muscles. Lesions may be recognized by the presence of **atrophy of these muscles and weakness of the first 15 degrees of abduction (supraspinatus) and of external rotation of the arm at the shoulder joint (infraspinatus).** The latter muscle is tested by having the patient flex the forearm and then, pinning the elbow to the side, asking him to swing the forearm backward against resistance. This nerve is often involved as a result of a **herniated CS-C6 disc** or as part of a **brachial plexus Neuropathy** of either the sporadic or inherited type. It may be affected during **infectious illnesses** and may be injured in gymnasts, or as a result of local pressure from carrying heavy objects on the shoulder (“**meatpacker’s neuropathy**")

Answer 49

** Axillary nerve** Axillary Nerve This nerve arises from the **posterior cord of the brachial plexus (mainly from the C5** root, with a smaller contribution from C6) and supplies the **teres minor and deltoid muscles**. It may be involved in **dislocations of the shoulder joint, fractures of the neck of the humerus, disc protrusion, and brachial neuritis**; in other instances, no cause may be apparent. The anatomic diagnosis depends on recognition of **paralysis of abduction of the arm** (in testing this function, the angle between the side of the chest and the arm must be **greater than 15 degrees and less than 90 degrees**), **wasting of the deltoid muscle, and slight impairment of sensation over the outer aspect of the shoulder**. קצת על המסיחים האחרים * The **dorsal scapular nerve** provides motor innervation to the **rhomboid** major and rhomboid minor muscles. In addition, it supplies the **levator scapulae muscle** along with the branches arising from spinal nerves C3 and C4. The rhomboids serve to pull the scapula posteriorly medially towards the vertebral column, while the levator scapulae elevates the scapula. * **Long Thoracic Nerve** (of Bell) This nerve is derived from the **fifth, sixth, and seventh** cervical nerves and supplies the **serratus anterior** muscle, which fixates the lateral scapula to the chest wall. Paralysis of this muscle results in an **inability to raise the arm over the head and winging of the medial border of the scapula when the outstretched arm is pushed forward against resistance**. ## Footnote Weakening of the muscles that fix the scapulae to the thorax (serratus anterior, lower trapezius, rhomboids) causes winging of the scapulae,

Answer 50

winging of scapula בהושטת הידיים הצידה A complete **lesion of the accessory nerve** results in **weakness of the sternocleidomastoid muscle and upper part of the trapezius** (the lower part of the trapezius is innervated by the third and fourth cervical roots through the cervical plexus). *Weakness can be demonstrated by asking the patient to **shrug his shoulders***; the affected side will be found to be weaker, and there will often be evident **atrophy of the upper part of the trapezius**. With the **arms at the sides, the shoulder on the affected side *droops* and the *scapula is slightly winged***; the latter defect is accentuated with lateral movement of the arm (with serratus anterior weakness, winging of the scapula is more prominent and occurs on forward elevation of the arm). When the patient turns his head forcibly against the examiner 's hand, preferably starting with the head deviated to the opposite side, the **sternocleidomastoid of the opposite side does not contract** firmly beneath the fingers.

Answer 51

בליטה של סקופלה בעת הרמת ידיים לצדדים

Answer 52

supra scapular nerve **Suprascapular Nerve** This nerve is derived from the **fifth (mainly) and sixth** cervical nerves and supplies the **supraspinatus and infraspinatus** muscles. Lesions may be recognized by the presence of **atrophy of these muscles and weakness of the first 15 degrees of abduction (supraspinatus) and of external rotation of the arm at the shoulder joint (infraspinatus).** The latter muscle is tested by having the patient flex the forearm and then, pinning the elbow to the side, asking him to swing the forearm backward against resistance. This nerve is often involved as a result of a **herniated CS-C6 disc** or as part of a **brachial plexus Neuropathy** of either the sporadic or inherited type. It may be affected during **infectious illnesses** and may be injured in gymnasts, or as a result of local pressure from carrying heavy objects on the shoulder (“**meatpacker’s neuropathy**") קצת על המסיחים האחרים- * brachial plexus- would expect more extensive disability * PIN- extension of radial nerve (C7-C8) in charge of supination and extension of wrist and fingers * long thoracic- serratus anterior muscle. will cause winged scapula

Answer 53

ברכיאל נויריטיס= parsonage turner **Parsonage Turner** This illness develops abruptly in an otherwise **healthy individual**; it may also *complicate an infection, an injection of vaccine or antibiotic, childbirth, surgical procedures of any type, or the use of **heroin***. Beginning as an **ache or deep burning in and around the shoulder that is centered over the deltoid**, at the root of the neck or in the axilla, and suspected at first of being only a muscle strain, the pain rapidly becomes very **intense** and may include a component of **burning**. The onset can be remarkably abrupt and occasionally awakens the patient from sleep. It is made worse by movements that involve the muscles in the region and the patient searches for a comfortable position. **Narcotics are usually required** to suppress the pain. After a period of several days there is a **rapid development of muscular weakness and thereafter, sensory and reflex impairment**. **With the development of weakness, the pain begins to subside.** Most of the neurologic deficits in our patients have been localized around the **shoulder and upper arm**. Either the **biceps or triceps reflex may be abolished**. In a few cases there has been an **additional median, radial, anterior, or posterior interosseous** nerve palsy that can be detected and isolated by EMG to a site distal to the plexus. Recovery of paralysis and restoration of sensation are usually complete in 6 to 12 weeks, but sometimes not for a year or longer.

Answer 54

1. elevated levels of LDL and cholesterol אינם חלק מבאסן קורנזוויג המוכר גם כ- abetalipoproteinemia **The initial symptoms, occurring between 6 and 12 years** (range: 2 to 20 years), are **weakness of the limbs with *areflexia* and ataxia of sensory** (tabetic) type, to which a **cerebellar component is added later**. **Steatorrhea**, raising the suspicion of celiac disease (sprue), often precedes the appearance of a weak and unsteady gait. Later, in more than half the patients, **vision may fail because of retinal degeneration** (similar to retinitis pigmentosa). **Kyphoscoliosis, pes cavus, and Babinski** signs are other elements in the clinical picture. The neurologic disorder is relatively **slowly progressive**-by the second to third decade, the patient is usually bedridden. The diagnostic laboratory findings are **spiky or thorny red blood cells (acanthocytes), low sedimentation rate, and a marked reduction in the serum of low density lipoproteins (LDL cholesterol, phospholipid, and ,beta-lipoprotein levels are all subnormal)**. Pathologic study has revealed the presence of **foamy, vacuolated epithelial cells in the intestinal mucosa** (causing absorption block); diminished numbers of myelinated nerve fibers in sural nerve biopsies, depletion of Purkinje and granule cells in all parts of the cerebellum; loss of fibers in the posterior columns and spinocerebellar tracts; loss of anterior horn and retinal ganglion cells and of muscle fibers and fibrosis of the myocardium.

Answer 55

Low levels of low density lipoproteins **Bassen Kornzweig – Abetalipoproteinemia** **The initial symptoms, occurring between 6 and 12 years** (range: 2 to 20 years), are **weakness of the limbs with *areflexia* and ataxia of sensory** (tabetic) type, to which a **cerebellar component is added later**. **Steatorrhea**, raising the suspicion of celiac disease (sprue), often precedes the appearance of a weak and unsteady gait. Later, in more than half the patients, **vision may fail because of retinal degeneration** (similar to retinitis pigmentosa). **Kyphoscoliosis, pes cavus, and Babinski** signs are other elements in the clinical picture. The neurologic disorder is relatively **slowly progressive**-by the second to third decade, the patient is usually bedridden. The diagnostic laboratory findings are **spiky or thorny red blood cells (acanthocytes), low sedimentation rate, and a marked reduction in the serum of low density lipoproteins (LDL cholesterol, phospholipid, and ,beta-lipoprotein levels are all subnormal)**. Pathologic study has revealed the presence of **foamy, vacuolated epithelial cells in the intestinal mucosa** (causing absorption block); diminished numbers of myelinated nerve fibers in sural nerve biopsies, depletion of Purkinje and granule cells in all parts of the cerebellum; loss of fibers in the posterior columns and spinocerebellar tracts; loss of anterior horn and retinal ganglion cells and of muscle fibers and fibrosis of the myocardium. שאר המסיחים- 2.Metachromatic Leukodystrophy 3.Bassen Kornzweig 4.Cerebrotendinous Xanthomatosis 5.Adrenoleukodystrophy

Answer 56

אובדן מיאלין פרוקסימלי **CMT**- Degenerative changes in the nerves result in depletion of the population of large sensory and motor fibers, leaving only the condensed endoneuria! connective tissue. As far as one can tell, **axons and myelin sheaths** are both affected, the **distal parts of the nerve more than the proximal ones**. In **type I**, the nerves may be enlarged, with **"onion-bulb“** formations of Schwann cells and fibroblasts, as in **Dejerine-Sottas disease (CMT3**; type III HMSN in the Dyck classification). This change can often be seen in sural nerve biopsies. **Anterior horn cells are slightly diminished in number **and some are **chromatolyzed** as a secondary change. **Dorsal root ganglion cells suffer a similar fate**. The disease **involves sensory posterior root fibers with degeneration of the posterior columns of **Goll** more than of **Burdach**. The **autonomic nervous system remains relatively intact**. The **muscles contain large fields of atrophic fibers (group atrophy)**. Some of the larger fibers have a target appearance and may show degenerative changes. All these muscle changes are typical of **neurogenic denervation** עוד מידע CMT **Clinical features** The early symptoms of **childhood clumsiness and athletic imprecision** are listed previously, to which are added **foot deformities of high arches and hammer toes**. There may have been **ankle fractures, foot-drop, medical plantar foot calluses** and a need for podiatric treatment at an early age, painless or foot ulcers. In adolescence, an “**inverted champagne bottle**” appearance of the forelegs may become apparent. The typical case of CMT has its **onset during late childhood or adolescence**, **CMT1** cases usually make their appearance during the **first decade** while the peak age of onset of **CMT2 is in the second**. **Both motor and sensory signs more severe in the *first* type***. **separation of the main subtypes on the basis of their electrophysiologic (EMG) features** and the discovery of **genetic mutations** that cause most of these diseases. most common type was the typical demyelinating variety of Charcot-Marie-Tooth disease (**CMT1A, 17p duplication**), The **chronic degeneration of peripheral nerves and roots results in *distal muscle atrophy beginning in the feet and legs* and later involving the hands**. The **extensor hallucis and digitorum longus, the peronei, and the intrinsic muscles of the feet are affected early in life** and this muscle imbalance produces the bony changes of pes cavus and pied en griffe (high arches and hammertoes). Later, all muscles of the legs and sometimes the lower third of the thigh become weak and atrophic. The thin legs have been likened to those of a stork or, if the lower thigh muscles are affected, to an inverted champagne bottle. Eventually the nerves to the calf muscles degenerate and the ability to plantar flex the feet is lost. After a period of many years, atrophy of the hand and forearm muscles develops in some cases. The hands later become clawed. The wasting seldom extends above the elbows or above the middle third of the thighs. Paresthesias and cramps are present but only to a slight degree and there is always some impairment, usually also mild, of deep and superficial sensation in the feet and hands, shading off proximally. Rarely, the sensory loss is severe and perforating ulcers appear as they do in the pure sensory varieties of inherited neuropathy. The **tendon reflexes are absent in the involved limbs**. The **Walking difficulty**, which is ultimately the main disability, is caused by a **combination of sensory ataxia and weakness**. **Foot-drop and instability of the ankles are additional handicaps** pain is unusual; the feet may become cool, swollen, and blue, secondary to inactivity of the muscles of the feet and legs and their dependent position. **The only distinguishing clinical feature between types 1 and 2, *enlargement of the nerves in type 1, most easily appreciated by palpation of the greater auricular and peroneal nerves.***

Answer 57

Connexin **the X- linked variant of CMT is the result of a mutation of the gene for connexin-32, another component of myelin** (GJB1= connexin). it is **X linked *Dominant*** עוד קצת על המסיחים האחרים * Anti GM1 Ab- **GBS**: A proportion of **axonal cases**, perhaps up to one-fifth, are associated with circulating antibodies to the **GM1 ganglioside** of peripheral nerve, and some of these reflect recently preceding infection with **C. jejuni**. The acronyms AMAN (acute motor) and AMSAN (acute motor-sensory axonal neuropathy) are equivalents to axonal GBS. Another variant of this illness, of which we have seen several instances, has been an **acute multifocal neuropathy** with electrophysiologic **motor conduction block** that leaves the reflexes unaltered and has high titers of **anti-GM1 antibody**. * Deletion of PMP22- The condition of hereditary liability to pressure palsies (**HNPP**) also displays an aberration on **chromosome 17**, but in the form of a **deletion** rather than a duplication of the gene for **PMP22**. * Duplication of PMP22- The most prevalent form of the disease is **CMT1A**, which displays an **autosomal dominant pattern** of inheritance with almost **complete penetrance**; it is due to **duplication of PMP 22** on **chromosome 17**. * Anti MAG Ab- **MGUS**, benign monoclonal gammopathy Although more than a dozen specific antibodies against myelin and other components of nerve have been identified among the paraproteins, the ones that give rise to the most distinctive clinical syndromes, present in 50 to 75 percent of patients with IgM-associated neuropathies, are those that react with a **MAG**, related glycolipids,. **Proprioceptive sensory loss with gait imbalance, tremor, and the Romberg sign are typical findings** in the group with anti-MAG activity, while **weakness and atrophy tend to appear later in the illness**.

Answer 58

False **Charcot-MarieTooth** (CMT) disease (**type 1**) shows **slowed nerve conduction** as a consequence of a disorder of **myelin**. A distinctive feature of hereditary neuropathy is the ***uniformity of the electrophysiologic changes***, e.g., a similar degree of slowing of nerve conduction velocity in all the nerves, a feature that distinguishes this group from most acquired neuropathies. The distinction between the **demyelinating and axonal types of inherited neuropathies** is based on the **motor nerve** (typically ulnar or median nerve) conduction velocities in the arms, with **slowing to velocities below 38 m/ s defining the demyelinating** category. * CMT1 – Demyelinating * CMT2 – Axonal * CMT3 - Congenital Hypomyelinating * CMT4 - Recessive The early symptoms of **childhood clumsiness and athletic imprecision** are listed previously, to which are added **foot deformities of high arches and hammer toes**. There may have been **ankle fractures, foot-drop, medical plantar foot calluses** and a need for podiatric treatment at an early age, painless or foot ulcers. In adolescence, an “**inverted champagne bottle**” appearance of the forelegs may become apparent. The typical case of CMT has its **onset during late childhood or adolescence**, **CMT1** cases usually make their appearance during the **first decade** while the peak age of onset of **CMT2 is in the second**. **Both motor and sensory signs more severe in the *first* type***. **separation of the main subtypes on the basis of their electrophysiologic (EMG) features** and the discovery of **genetic mutations** that cause most of these diseases. most common type was the typical demyelinating variety of Charcot-Marie-Tooth disease (**CMT1A, 17p duplication**), The **chronic degeneration of peripheral nerves and roots results in *distal muscle atrophy beginning in the feet and legs* and later involving the hands**. The **extensor hallucis and digitorum longus, the peronei, and the intrinsic muscles of the feet are affected early in life** and this muscle imbalance produces the bony changes of pes cavus and pied en griffe (high arches and hammertoes). Later, all muscles of the legs and sometimes the lower third of the thigh become weak and atrophic. The thin legs have been likened to those of a stork or, if the lower thigh muscles are affected, to an inverted champagne bottle. Eventually the nerves to the calf muscles degenerate and the ability to plantar flex the feet is lost. After a period of many years, atrophy of the hand and forearm muscles develops in some cases. The hands later become clawed. The wasting seldom extends above the elbows or above the middle third of the thighs. Paresthesias and cramps are present but only to a slight degree and there is always some impairment, usually also mild, of deep and superficial sensation in the feet and hands, shading off proximally. Rarely, the sensory loss is severe and perforating ulcers appear as they do in the pure sensory varieties of inherited neuropathy. The **tendon reflexes are absent in the involved limbs**. The illness progresses very slowly over decades, giving the impression of stabilization for long periods. The **Walking difficulty**, which is ultimately the main disability, is caused by a **combination of sensory ataxia and weakness**. **Foot-drop and instability of the ankles are additional handicaps** pain is unusual; the feet may become cool, swollen, and blue, secondary to inactivity of the muscles of the feet and legs and their dependent position. **The only distinguishing clinical feature between types 1 and 2, *enlargement of the nerves in type 1, most easily appreciated by palpation of the greater auricular and peroneal nerves.*** CMT is divided into the two broad types based on the speed of motor nerve conduction in the ulnar or median nerves, as mentioned, slow (mean **conduction velocity less than 38 m/s** but often in the range of 20 m/s) in **type 1**, and **normal or near-normal conduction in type 2**. Electromyographers appropriately refer to these, respectively, as the **demyelinating and axonal types**. In both, the compound muscle action potentials and sensory potentials are greatly reduced in amplitude, but in **type 2 there are findings of denervation** in the EMG. In **type 1 there is severe and widespread slowing** of nerve conduction, but the **electrical conduction block that characterizes acquired demyelinating neuropathies is not found.**

Answer 59

**the X- linked variant of CMT is the result of a mutation of the gene for connexin-32, another component of myelin** (GJB1= connexin). it is **X linked *Dominant***

Answer 60

Charcot-Marie-Tooth disease

Answer 61

לחץ על הפרונאל

Answer 62

4. נוירופתיה על רקע לחץ פרונאלי באזור ראש הפיבולה compression neuropathy due to loss of fat pad

Answer 63

2. conduction block in the peroneal nerve at the fibular head compression neuropathy

Answer 64

נגע אוסטאוסקלרוטי בעצמות ארוכות. **POEMS Syndrome**, A neuropathy associated with **multiple myeloma**. it complicates **13 to 14 percent** of cases of multiple myeloma and has a disproportionately **high association with the osteosclerotic Form** of the disease. An **abnormal monoclonal globulin** (mainly with the kappa light chain component in multiple myeloma but **lambda** in the osteosclerotic type) is found in the serum of more than 80 percent of patients with myelomatous neuropathy. In a special and small group of patients with osteosclerotic myeloma, there is a predominantly demyelinating **sensorimotor polyneuropathy** and systemic disease termed POEMS (i.e., **polyneuropathy** of moderate severity is associated with **organomegaly, endocrinopathy, elevated M protein, and skin changes**, mainly hypertrichosis and skin thickening). The presence of the disease can be suspected from the presence of **demyelinating** features on the nerve conduction studies, an **immunoglobulin spike** in the blood, sometimes **polyclonal or biclonal** rather than monoclonal and, as mentioned, possessing a **lambda light chain** component. The **diagnosis requires the demonstration of one or more osteosclerotic lesions** by a radiographic survey of the long bones, pelvis, spine, and skull as well as a PET study; which usually shows the osteosclerotic lesions as highly active (a bone scan is insensitive) **and a bone marrow examination**, which shows a **moderate increase in the number of well-differentiated plasma cells**. In most of our patients there have been several discrete bone lesions concentrated in the ribs and spine; the skull and long bones may harbor such lesions as well, or there may be a single lesion, which is often situated in the spinal column. Biopsy of a bone lesion is justified. The organomegaly and skin changes are apparently the result of high levels of circulating VEGF that is produced by the tumor and is useful in confirming the diagnosis.

Answer 65

True **Tangier Disease (ABC1 Mutation)** This is a **rare, familial, small fiber** neuropathy, inherited as an **autosomal recessive** trait. The mutation **eliminates the function** of the adenosine triphosphate (ATP)cassette transporter protein, **ABC1**. It results in a **deficiency of high density lipoprotein**, **extremely low serum cholesterol**, and **high triglyceride** concentrations in the serum. Perhaps on the basis of these abnormalities, the patients are disposed to **early and severe atherosclerosis**. The presence of enlarged,yellow-orange (**cholesterol laden) tonsils** is said to be a frequent manifestation (of course, previous tonsillectomies obviate this sign). About half of the reported cases have had neuropathic symptoms, taking the form of an **asymmetrical sensorimotor neuropathy that fluctuates in severity**. The sensory loss is predominantly for **pain and temperature** and extends over the entire body; at times it is limited to the face and upper extremities, simulating syringomyelia (“**pseudosyringomyelia**”). Tactile and proprioceptive sensory modalities tend to be **preserved**. The polyneuropathy may come in **attacks**—that is to say, it simulates a recurrent process. Muscular weakness, if present, affects either the lower or upper extremities or both, particularly the **hand muscles**, which may undergo **atrophy and show denervation** by EMG. In a small number of patients there has been **facial diplegia** out of proportion to weakness elsewhere. **Tendon reflexes are often lost or diminished.** Transient **ptosis and diplopia** have been reported. **Nerve conduction is slowed**. Fat laden macrophages are present in the bone marrow and elsewhere. No complete pathologic studies are available. There is no known treatment but dietary measures to reduce triglycerides may help, particularly in preventing atherosclerosis but the influence on the neuropathy is uncertain.

פרק 43 Chapter 43: Diseases of the Peripheral Nerves Flashcards

(92 cards)