פרק 39 Chapter 39: The Acquired Metabolic Disorders of the Nervous System Flashcards
איזו מן המחלות/תופעות הבאות אינה מתוארת עם תירוטוקסיקוזיס
1. simple proximal myopathy
2. myasthenic syndrome
3. periodic paralysis
4. myasthenia gravis
5. external opthalmoplegia
- myashtenic syndrome
Diseases related to thyroid function:
1. Chronic thyrotoxicmyopathy – progressive weakness and wasting of skeletal muscles – pelvic girdle and thighs typically. CPK not increased and EMG normal
2. Exopthalmicopthalmoplegia – in asscoiation with graves disease
3. Myasthenia gravis 5% of MG patients have hyperthyroidism
4. Periodic paralysis – closely resembles familial hypokalaemic paralysis
Muscle hypertrophy and slow muscle contraction and relaxation
Table 39-1
CLASSIFICATION OF THE ACQUIRED METABOLIC
DISORDERS OF THE NERVOUS SYSTEM IN ADULTS(4)
Presenting as confusion, stupor or coma (11)
Presenting as progressive extrapyramidal syndrome (3)
Presenting as cerebellar ataxia (3)
Presenting as psychosis or dementia (4)
מה מאפיין
hashimoto thyroiditis?
1. antibodies against thyroid peroxidase in the CSF.
2. תפקודי תריס תקינים
3. תפקודי תריס מופרעים.
antibodies against thyroid peroxidase in the CSF
Hashimoto-
It is important to note that most have had normal thyroid function. There are in these cases, however, high titers of several antithyroid antibodies, particularly antibodies against thyroid peroxidase and thyroglobulin; some affected individuals have more than one such antibody. Ferracci and colleagues found evidence of the production of these antibodies in the nervous system and of their presence in spinal fluid. One must be cautious, however, in interpreting the presence of antithyroid antibodies in the blood, as they are detected in many people without an encephalopathy, particularly older women, and in two-thirds of patients with Graves disease. The most commonly observed syndrome is of confusion or stupor accompanied by multifocal myoclonus. Seizures-including myoclonic and rarely, nonconvulsive status epilepticus. Hemiparesis, ataxia, psychosis, and unusual tremors, including those of the palate, have been reported in individual cases as in the series reported by Castillo and colleagues; they found tremor, transient aphasia, myoclonus, ataxia and seizures to be present in that order of frequency. Many had liver function abnormalities and one-fifth showed inflammatory changes in the CSF. Some of the reports included children.
איש עובד במוסך מתלונן על התקפים של כאב ראש ובלבול. מה ההרעלה?
1. פחמן חד חמצני
2. נתרן חד חמצני
3. tension headache
4. פסיכוגני
פחמן חד חמצני
CO poisoning:
* Early: headache, nausea, dyspnea, confusion, dizziness, clumsiness
- Cherry red colour of skin
- Cyanosis
- High levels: blindness, visual field defects, papillaedema
- Higher levels: coma, decerebrat, decorticate, seizures.
- Delayed neurological deterioration: Extrapyramidal features,
Discrete lesions in GP bilaterally characteristic
מטופל שחולץ מחוסר הכרה מבית סגור עם תנור נפט דולק, מה נראה בהדמיה
1. נגעים בפלידום דוצ
2. גזע מוח
3. קורטיקלי
נגעים בפלידום דו”צ
CO poisoning:
* Early: headache, nausea, dyspnea, confusion, dizziness, clumsiness
- Cherry red colour of skin
- Cyanosis
- High levels: blindness, visual field defects, papillaedema
- Higher levels: coma, decerebrat, decorticate, seizures.
- Delayed neurological deterioration: Extrapyramidal features,
Discrete lesions in GP bilaterally characteristic
קשישה הובאה למיון בשל ישנוניות וכאבי ראש, לאחר שישנה עם תנור נפט דולק בחדר סגור. איזה
מבנה מבין הבאים ייראה פגוע ספציפית בבדיקת
MRI במקרה זה?
א. Putamen
ב. Subthalamic nucleus
ג. Caudate
ד. Globus pallidum
גלובוס פלידום
CO poisoning:
* Early: headache, nausea, dyspnea, confusion, dizziness, clumsiness
- Cherry red colour of skin
- Cyanosis
- High levels: blindness, visual field defects, papillaedema
- Higher levels: coma, decerebrat, decorticate, seizures.
- Delayed neurological deterioration: Extrapyramidal features,
Discrete lesions in GP bilaterally characteristic
מהו הטיפול התרופתי המניעתי למחלת גבהים?
אצטזולמיד ודקסמטזון.
מה לא יעזור תאורטית בהיפוקסיה?
א.הורדה של טמפרטורת הגוף
ב.induced hypoglycemia
ג.100%חמצן
היפוגליקמיה אינה טיפול להיפוקסיה.
היפוטרמיה
Attempts to ameliorate brain injury by the use of hypothermia, a technique that has met with success in adult cardiac arrest, have given conflicting results.
Much attention was drawn to the randomized trials conducted by Bernard and colleagues and by the Hypothermia After Cardiac Arrest Study Group, of mild hypothermia applied to unconscious patients immediately after cardiac arrest. They reduced the core temperature to 33°C (91 °F) within 2 h of the arrest and sustained this level for 12 h in the first trial, and between 32°C and 34°C for 24 h in the second study. Both trials demonstrated improved survival and better cognitive outcome in survivors, compared to leaving the patient in a normothermic state and this led to the development of guidelines and a change in clinical practice in the U.S. and elsewhere after 2002.
The use of high-dose barbiturates has not met with the same success.
בן 63 עם פגיעה מוחית אנוקסית משנית להחייאה ממושכת. בבדיקתו בזמן תנועה של הידיים נצפו
קפיצות חדות של קבוצת שרירים. איזה טיפול ישפר את ההפרעה בתנועה ?
א. Botulinum toxin
ב. Haloperidol
ג. Levodopa
ד. Valproic acid
valproic acid
Postanoxic Intention (or Action) Myoclonus
This type of myoclonus was described by Lance and Adams myoclonus is a localized, stimulus-evoked myoclonus. Speech may be fragmented by the myoclonic jerks, and a syllable or word may be almost compulsively repeated, as in palilalia. Myoclonus of the axial muscles may make walking impossible.
Action myoclonus is almost always associated with cerebellar ataxia. The pathologic anatomy has not been entirely ascertained.
Barbiturates and valproic acid have been helpful in some cases. levetiracetam may be useful 5-hydroxytryptophan alone or in combination with tryptophan or other drugs had been recommended in the past (van Woert et al). A combination of several of these medications is usually required to make the patient functional
מטופל ששוכב בטיפול נמרץ לב לאחר החייאה וסובל מנזק מוחי אנוקסי מפתח תנועות חדות בארבע גפיים. מה טיפול?
1. קלונקס
2. פניטואין
3. גאבאפנטין
4. ויגאבאטרין
קלונקס
תאור של חולה אחרי החייאה לבבית, הגיע לביקורת אחרי חודש. למה לא תצפו:
1. בלינט
2. פרקסינסוניזם
3. אטקסיה צרבלרית
4. מיאלופתיה
לא נצפה למיאלופתיה מכיוון שחוט השדרה וגזע המוח יחסית עמידים לנזק אנוקסי
Posthypoxic Neurologic Syndromes
The permanent neurologic sequelae or posthypoxic syndromes observed most frequently are as follows:
1. Persistent coma or stupor, described above
2. With lesser degrees of cerebral injury,dementia with or without extrapyramidal signs
3. Extrapyramidal (parkinsonian) syndrome with cognitive impairment (discussed in relation to CO poisoning)
4. Choreoathetosis
5. Cerebellar ataxia
6. Intention or action myoclonus (Lance-Adams syndrome)
7. An amnesic state
If hypoperfusion dominates, the patient may also display the manifestations of watershed infarctions that are situated between the end territories of the major cerebral vessels. The main syndromes that become evident soon after the patient awakens are as follows:
1. Visual agnosias including Balint syndrome and cortical blindness (Anton syndrome) (see Chap. 21), representing infarctions of the watershed between the middle and posterior cerebral arteries (see Fig. 39-2)
2. Proximal arm and shoulder weakness, sometimes accompanied by hip weakness (referred to as a “person [man]-in-the-barrel” syndrome), reflecting infarction in the territory between the middle and anterior cerebral arteries. These patients are able to walk, but their arms dangle and their hips may be weak.
The two watershed syndromes may rarely coexist. The interested reader may consult the appropriate chapter in the text on neurologic intensive care by Ropper and colleagues for further details. There are also watershed areas in the spinal cord (Chap. 42).
Seizures may or may not be a problem, and when present are often resistant to treatment. Well-formed motor convulsions are infrequent. Myoclonus is more common and may be intermixed with fragmentary convulsions. Myoclonus is a grave sign in most cases but it generally recedes after several hours or a few days. These movements are also difficult to suppress, as noted further on.
Delayed Posthypoxic Encephalopathy and Leukoencephalopathy
This is a relatively uncommon and unexplained phenomenon. Initial improvement, which appears to be complete, is followed after a variable period of time (1 to 4 weeks in most instances) by a relapse, characterized by apathy, confusion, irritability, and occasionally agitation or mania. Most patients survive this second episode, but some are left with serious mental and motor disturbances (Choi; Plum et al). In still other cases, there appears to be progression of the initial neurologic syndrome with additional weakness, shuffling gait, diffuse rigidity and spasticity, sphincteric incontinence, coma, and death after 1 to 2 weeks. Exceptionally, there is yet another syndrome in which an episode of hypoxia is followed by slow deterioration, which progresses for weeks to months until the patient is mute, rigid, and helpless. In such cases, the basal ganglia are affected more than the cerebral cortex and white matter as in the case studied by our colleagues Dooling and Richardson. Instances have followed cardiac arrest, drowning, asphyxiation, and carbon monoxide poisoning.
The imaging features of the white matter disorder can be quite striking (Fig. 39-4). A mitochondrial disorder has been suggested, on uncertain grounds, as the underlying mechanism.
structures of the brainstem and spinal cord are relatively resistant to anoxia and hypotension and stop functioning only after the cortex has been badly damaged
נער בן 13 מטופל במחלקה לטיפול נמרץ לאחר טביעה ממושכת עם נזק מוחי . איזה אזור במוחו עלול להיפגע לפני אזורים אחרים?
א. Basal ganglia
ב. Hippocampus
ג. Red nucleus
ד. Watershed cortical areas
The pathologic effects of ischemic brain injury from systemic hypotension differ from those caused by pure anoxia. Under conditions of transient ischemia, one pattern of damage takes the form of incomplete infarctions in the border zones between major cerebral arteries
With predominant anoxia, neurons in portions of the hippocampus and the deep folia of the cerebellum are particularly vulnerable. More severe degrees of either ischemia or hypoxia, or the combination, lead to selective damage to certain layers of cortical neurons, and if more profound, to generalized damage of all the cerebral cortex, deep nuclei, and cerebellum.
structures of the brainstem and spinal cord are relatively resistant to anoxia and hypotension and stop functioning only after the cortex has been badly damaged
process may be affected by massive calcium influx through a number of different membrane channels, which activates various kinases that participate in the process of gradual cellular destruction
one of the reasons for the irreversibility of ischemic lesions may be swelling of the endothelium and blockage of circulation into the ischemic cerebral tissues, the “no-reflow”.
here is also a poorly understood phenomenon of delayed neurologic deterioration after anoxia; this may be a result of the blockage or exhaustion of some enzymatic process during the period when brain metabolism is restored.
מהו מנגנון הפיצוי הנוסף המופעל בשלב של ירידת לחץ הזילוח (פרפוזיה) במוח מתחת ל60-70 מ”מ
כספית:?
א. הגברת תפוקת הלב (cardiac output) .
ב. הרחבת כלי דם במנגנון
auto regulation בעורקי המוח.
ג. הגדלת ה
oxygen extraction
מהדם המגיע למוח
ד. היפרגליקמיה משנית להפרשת
adrenaline מוגברת.
הגדלת ה
oxygen extraction
פיזיולוגיה של נזקפיזיולוגיה של נזק איסכמי והיפוקסי
מספר מנגנונים הומאוסטטים מגינים על המח מפני נזק היפוקסי ואיסכמי: 1) אוטורגולציה: דילטציה קומפנסטורית של כל”ד בתגובה לירידה בפרפוזיה מוחית
2) כאשר לחץ הזילוח יורד מתחת 60-70 מ”מ/כספית, תחל גם
increased oxygen extraction
כמנגנון קומפנסטורי נוסף.
באיסכמיה גלובלית של המח, הרקמה “מרוקנת” ממשאבי האנרגיה שלה תוך 5 דקות (בתנאי היפותרמיה הזמן ממושך יותר).
3) כשהסיבה למחסור באנרגיה היא היפוקסיה, תהיה עליה בזרימת הדם.
בPCO2 של 25 mmHg,
העליה בCBF היא של כ-400%.
עליה דומה מתרחשת עם ירידה של המוגלובין ל20% מהנורמה.
בן 10 מנותח ונכנס להלם המורגי במהלך הניתוח עם ירידה ממושכת של זרימת דם למוח . לאחר
שמצבו התייצב והתעורר מהניתוח מתלונן על חולשה.
במצב זה, איזו תבנית של חולשת שרירים שכיחה יותר ?
א. חולשה בשרירים האינטרינזיים בכף היד וכף הרגל.
ב. חולשה בשרירי חגורת הכתף והזרוע ובכיפוף הירך.
ג. המיפרזיס אטקטית
(ataxic hemiparesis) .
ד. חולשת אקסטנסורים של האמה, כף היד וכף הרגל.
ב. חולשה בשרירי חגורת הכתף והזרוע ובכיפוף הירך
man in a barrel
בגלל פגיעה ב
watershed areas of MCA& ACA
If hypoperfusion dominates, the patient may also display the manifestations of watershed infarctions that are situated between the end territories of the major cerebral vessels. The main syndromes that become evident soon after the patient awakens are as follows:
1. Visual agnosias including Balint syndrome and cortical blindness (Anton syndrome) (see Chap. 21), representing infarctions of the watershed between the middle and posterior cerebral arteries (see Fig. 39-2)
2. Proximal arm and shoulder weakness, sometimes accompanied by hip weakness (referred to as a “person [man]-in-the-barrel” syndrome), reflecting infarction in the territory between the middle and anterior cerebral arteries. These patients are able to walk, but their arms dangle and their hips may be weak.
מה הפתולוגיה שניתן למצוא ב
hepatic coma
א. נוירונים מסוג
Alzheimer type 2
ב. שינוי ב
basement membrane
של קפילרות
נוירונים מסוג אלצהיימר סוג 2
Pathogenesis of Hepatic Encephalopathy
The most plausible hypothesis relates hepatic coma to an abnormality of nitrogen metabolism, wherein ammonia, which is formed in the bowel by the action of urease-containing organisms on dietary protein, is carried to the liver in the portal circulation but fails to be converted into urea because of hepatocellular disease, portal–systemic shunting of blood, or both. As a result, excess NH3 reaches the systemic circulation, where it interferes with cerebral metabolism in a way that is not fully understood. The ammonia theory best explains the basic neuropathologic change. Because the brain is lacking in urea cycle enzymes, Norenberg has proposed that the hypertrophy of the astrocytic cytoplasm (Alzheimer type 2 astrocytes) and proliferation of mitochondria and endoplasmic reticulum, as well as the increase in the astroglial glutamic dehydrogenase activity, all reflect heightened metabolic activity of these systems within astrocytes associated with ammonia detoxification. Removal of brain ammonia depends on the formation of glutamine, a reaction that is catalyzed by the ATP-dependent enzyme glutamine synthetase, which is compartmentalized to astrocytes. It has been shown in experimental animals that hyperammonemia leads to a depletion of ATP in midbrain reticular nuclei. Whether this is the primary cause of cerebral dysfunction has not been resolved.
מה יימצא בהדמיהבאנצפלופתיהכבדית?
1. גלובוספלידוסדו”צהאדרה בT1
2. אטרופיהקורטיקלית
3. אטרופיה של ראההקאודייט
האדרה של הגלובוס פלידוס דו”צ
בT1
MRI יראה היפר-אינטנסיות ב-globus pallidus
כנראה בשל משקעי
manganese.
בבדיקה פתולוגית בנתיחה לאחר המוות של מוחו של חולה עם הפרעה קוגניטיבית מתקדמת על פני
מספר שנים, נמצא ריבוי אסטרוציטים גדולים עם צביעת PAS
חיובית וריבוי מיטוכונדריה, בשכבות
העמוקות של הקורטקס, בגרעין הלנטיפורמי, תלמוס, substantia nigra
.מהי האבחנה הסבירה?
א. Chronic hepatic encephalopathy .
ב. Dentatorubral-pallidoluysian atrophy (DRPLA) .
ג. Dialysis dementia .
ד. Lewy body dementia
chronic hepatic encephalopathy
Neuropathologic Changes
בחולים שמתו מקומה הפטית, נמצאו בפתולוגיה עליה בגודל ומספר של אסטרוציטים פורטו-פלזמטים בשכבות עמוקות של הקורטקס, גרעין לנטיקולרי, תלמוס, סובסטנציה ניגרה, קורטקס צרבלרי, גרעינים פונטינים,רד נוקלאוס, ודנטייט נוקלאוס. ללא שינוי בתאי עצב.
בצביעת PAS - Alzheimer type II astrocytes –
תאי גליה (אסטורציטים פורטו-פלזמטים) לא תקינים המכילים גופי הסגר של גליקוגן ונראים גם בווילסון. מאפייניהם: התנפחות של הטרמינל פרוסס, וקולות ציטופלזמטיות, ועליה במיטוכונדריה ואנזימים המבצעים קטבוליזם של אמוניה. בנוסף נמצא ניוון מסוים של סיבים עטופי מיאלין בנויטרופיל ועליה בציטופלזמה של אוליגודנדרוציטים. במקרים כרוניים, יש גם אובדן נוירונים בשכבות העמוקות של קורטקס, קורטקס צרבלרי, וגרעין לנטיקולרי, וכן וקואליזציה של הרקמה (דומה לנגעים בווילסון).
השינויים בתאים אסטרוציטים מתרחשים בכל חולי אנצפלופתיה כבדית בדרגה מסוימת (ייתכן כי גורמים להפרעה בפעילות סינפטית). השינויים בתאי הגליה נמצאים בקורלציה למשך המחלה.
נוירופתיה והפרעה צרבלרית
Celiac Sprue:
* Neuropathy
* Polymyoclonus
* Progressive cerebellar ataxia
* myelopathy
* Encephalopathy
* Dementia
* Psychiatric symptoms
* Spinocerebellar syndrome
* Association with HLA DQ2
The situation is further complicated by the finding
that antigliadin antibodies (which are not autoantibodies but are directed against gluten, the offending agent), while not specific for celiac disease, do correspond to the presence of neurologic manifestations (ataxia and neuropathy);
however, the more specific antiendomysium
and antitransglutarninase autoantibody markers of sprue have little apparent relation to the presence of neurologic disease. Even more confusing is the claim that half of these patients will have one or another antibody but no clinical enteropathy, making it necessary to perform a small-bowel biopsy to detect villous atrophy
דיפלופיה אינו סימן של צליאק
Celiac Sprue:
* Neuropathy
* Polymyoclonus
* Progressive cerebellar ataxia
* myelopathy
* Encephalopathy
* Dementia
* Psychiatric symptoms
* Spinocerebellar syndrome
* Association with HLA DQ2
מה מההפרעות המטבוליות הבאות גורמת לסימניםפוקאלים?
1. היפונתרמיה
2. היפראמומנמיה
3. היפרגליקמיה
4. היפוקלצמיה
היפרגליקמיה
שינוי התנהגותי
Diffuse muscle weakness or muscle twitching, spasms, and cramps should always raise the question of uremia or an abnormality in serum electrolytes. These disorders reflect the concentrations of electrolytes in the intra- and extracellular fluids. If the
* plasma concentration of K falls below 2.5 mEq/L or rises above 7 mEq/L, weakness of extremity and trunk muscles results; below 2 mEq/L or above 9 mEq/L, there is almost always flaccid paralysis of these muscles and later, of the respiratory ones as well; only the extraocular and other cranial muscles are
Spared. In addition, the tendon reflexes are diminished or absent. The normal reaction of muscle to direct percussion is also reduced or abolished, suggesting impairment of transmission along the sarcolemmal membranes themselves.
* Hypocalcemia of 7 mg/dL or less (as in rickets or hypoparathyroidism) or relative reduction in the proportion of ionized calcium (as in hyperventilation) causes increased muscle irritability and spontaneous discharge of sensory and motor nerve fibers (i.e., tetany) and sometimes convulsions from similar effects upon cerebral neurons; frequent repetitive and prolonged spontaneous discharges grouped in couplets or triplets appear in the EMG.
* Hypercalcemia with Ca levels above 12 mg/ dL (as occurs in vitamin D intoxication, hyperparathyroidism, carcinomatosis, sarcoidosis, and multiple myeloma) causes weakness perhaps on a central basis, and lethargy.
* Extreme hypophosphatemia, observed most often with intravenous hyperalimentation or bone tumor, can cause acute areflexic paralysis with nerve conduction abnormalities.
* Reduction in the plasma concentration of magnesium also results in tremor, muscle weakness, tetanic muscle spasms, and convulsions;
a considerable increase in magnesium levels leads to muscle weakness and
depression of central nervous function. The weakness of muscle in hypermagnesemia may also be partly a result of reduced release of ACh at the motor end plate.
היפרקלצמיה
כנראה בגלל אי ספיקת הכליות!
serum calcium concentration greater than 10.5 mg/ dL. If the serum protein content is normal, Ca levels greater than 12 mg/ dL are required to produce neurologic symptoms. However, with low serum albumin levels, an increased proportion of the serum Ca is in the unbound or ionized form (upon which the clinical effects depend), and symptoms may occur with total serum Ca levels as low as 10 mg/ dL.
In young persons, the most common cause of hypercalcemia is hyperparathyroidism (either primary or secondary);
in older persons, osteolytic bone tumors, particularly meta-static carcinoma and multiple myeloma, are often causative. Less-common causes are vitamin D intoxication, prolonged immobilization, hyperthyroidism, sarcoidosis, and decreased calcium excretion (renal failure).
* Anorexia, nausea and vomiting, fatigue, and headache are usually the initial symptoms, followed by confusion (rarely a delirium) and drowsiness, progressing to stupor or coma in untreated patients. A history of recent Constipation is common. Diffuse myoclonus and rigidity occur occasionally, as do elevations of spinal fluid protein (up to 175 mg/100 mL). Convulsions are uncommon.
מטופל צעיר עם פרכוסים והסתיידויות גרעיני בסיס, קלציום נמוך בדם.
1. היפופאראתירואידיזם
2. מחלת FAHR
3. האנטיגנטון
היפופארתירואידיזם=
צעיר+ קלציום נמוך+ הסתיידויות
היפונתרמיה 112 שתוקנה ל132 תוך 8 שעות ואז לפתע אובדן הכרה. מה יהיה בהדמיה?
1. הירפאנטסיות בגזע המח
2. פונס - batwing
3. בצקת מוחית
batwing פונס
Figure 39-1.
Axial CT without contrast 1 day after cardiac arrest demonstrating loss of distinction between gray and white matter structures throughout the cerebral hemispheres. The patient remained comatose and became vegetative.
Figure 39- 2.
Axial CT without contrast showing arterial borderzone infarctions between the middle and posterior cerebral arteries after brief cardiac arrest. The patient had Balint syndrome.
Figure 39-3.
Axial T2 weighted
MRI showing striatal damage after anoxia from suffocation. The pallidum is relatively spared, in contrast to typical cases of carbon monoxide poisoning (see Fig. 39-5).
Figure 39-3.
Axial T2 weighted
MRI showing striatal damage after anoxia from suffocation. The pallidum is relatively spared, in contrast to typical cases of carbon monoxide poisoning (see Fig. 39-5).
Figure 39-4.
Axial T2 fluid attenuated inversion recovery (FLAIR) MRI of delayed postanoxic leukoencephalopathy in a patient who had recovered after drowning and deteriorated 2 weeks later.
Figure 39-4.
Axial T2 fluid attenuated inversion recovery (FLAIR) MRI of delayed postanoxic leukoencephalopathy in a patient who had recovered after drowning and deteriorated 2 weeks later.
Figure 39-5.
Axial CT without contrast of a 30 year-old woman who attempted suicide by carbon monoxide inhalation. Small areas of decreased attenuation are
seen in the pallidum bilaterally (arrows). The only neurologic residua were a mild defect in retentive memory.
Figure 39-6.
T2-weighted MRI showing the typical lesion of central pontine myelinolysis in an alcoholic patient.
