(review in the Neurologist 2000; 6:205-13) author Jane Chan MD
Symptoms
1. In acute ON more than 90 % have loss of central vision. Occasionally patients get loss of peripheral vision to one side or superiorly or inferiorly.
2. Mild orbital pain above or behind the eye, preceding or concurrently with the visual loss, aggravated by upwards movement of the eye, and last up to several weeks. This may be due to triggering of trigeminal stimulation of the optic nerve sheath.
3. Less conmon symptoms are photophobia, dullness or loss of colors, perceptions of phosphenes (flashing lights with noise or eye movements) or decreased depth perception.
Signs
1. Visual loss worsens over hours, days or minutes and peaks within days to a week. Maximal return occurs within 3-6 months and does not correlate to initial visual loss.
2. Patterns of visual field loss was varied as central scotoma resolves to a small dim central or a paracentral deficit. Patterns include an arcuate scotoma, altitudinal scotoma (superior or inferior),peripheral constriction, central or cecocentral scotoma, bitemporal or hemianopic deficit. Patterns can vary day to day or hour to hour.
3. Color and contrast visionare reduced. The color defect is usually more severe than the acuity loss. The Farnsworth-Munsell 100 hue test is highly sensitive and specific. The short version with caps 22-42 has similar sensitivity for monitoring after ON. More blue yellow defects occur acutely, more red green defects occur after 6 months. Patients also have a decreased sensation of brightness.
4. RAPD is almost always present in acute ON; absence suggests optic neuropathy or other etiology.
5. Half of the patients in the ONTT had abnormal fellow eyes (contrateral) and many of these thought their vision contralaterally was normal.
6. PEARL-- RARELY an RAPD occurs in a retrochiasmal lesion due to pupillary fibers travelling together in optic tract
RED FLAGS or atypical features of optic neuritis
1. age greater than 50
2. Optic pallor at presentation
3. no pain
4. pain or vision loss that continues over weeks
5. poor visual recovery
6. associated systemic signs and symptoms
Tuesday, January 29, 2008
Tests for myasthenia gravis: Pearls
1. Tensilon test should be unequivocal and not subjective. In one study all patients who had a positive test responded in the first 7 mg.
2. False positive tensilon tests occurred in LEMS< GBS, compressive cranial neuropathies and brain stem lesions (Seminars of Neurology 2003, author Pascuzzi).
3. Muscarinic effects (tearing, sweating,cramping, salivating and nausea) are common. Relative contraindications are cardiac arrythmias and asthma. Cardiac monitoring may not be universally required.
4. A neostigmine methylsulfate injection can be used in children with a longer onset and offset (latter is 30 minutes) but may be harder to interpret.
5. The ice pack test of placing the ice pack on for 2-5 minutes has reported high sensitivity and specificity but may be hard to tolerate for patients (Golnick AC et al. Opthalmology 1999 186:1282-6). The mean improvement with this test is 4.5 mm.
6. The rest test (close eyes for 3 minutes) results in a mean improvement of 2 mm of ptosis.
7. The sleep test (30 minutes) shows improvement in all Tensilon positive patients plus two others (out of 42 tested).
8. Lab tests of binding Ach receptors is positive in 50 % of OM patients (v. 90 % of MG patients overall); blocking antibodies add only another 1 percent sensitivity, and modulating antibodies actually do improve sensitivity slightly but also have more false positives. see Howard FJ et al. NY Acad Sci 1987; 505: 526-538).
9. False positive conditions with ACH receptor antibodies (again from Howard et al.) are: AI hepatitis, SLE, ALS, inflammatory neuropathies, LEMS, thyroid opthalmopathy, 1 degree relatives of MG patients, thymoma, RA, and patients taking penicillamine.
10. Striated muscle ab's as a marker for thymoma: they predict thymoma in patients with MG under 40 (80%) and thymoma in nonmyasthenics (positive in 25 % of those). False positives are seen in RA treated with penicillamine, LEMS, Bone marrow graft recipients, GVHD, and paraneoplastic disease (see Lennon, Neurol suppl 5, 1997 S23-27).
11. De Graefe's test 12. Mary Walker phenomenon-- inflation of cuff above normal systolic pressure causes fatigue. Deflation of the cuff causes exacerbation of MG in rest of the body
13. Fatigue-ability is the hallmark of MG. Test for with sustained upgaze test 30-60 sec (especially check medial rectus muscle> superior and lateral recti); sustained abduction of the arms (120 s); sustained elevation of the leg while lying supine (90 sec); repeated rising from a chair without using arms, up to 20 times, look for bfm's; counting aloud to 50.
14. The rare patient that presents with isolated respiratory involvement may have orthopnea, ie SOB while lying down.
15. Enhanced ptosis of contralateral side may occur with manual elevation of one ptotic lid
16. Unilateral frontal hypercontraction is a sign of weak lids.
17. Specific muscles to assess in suspected MG include eom's, oropharyngeal, facial, respiratory, axial and limb
18 Pseudo INO occurs when adducting eye does not adduct and abducting eye has nystagmus
19. Cover - uncover test can reveal weakness if done repeatedly.
20. Beware of holding target to fixate too close, will reveal a convergence abnormality rather than a true EOM abnormality.
21. Look for snarl with attempt to smile, inability to pucker to kiss
22. Pattern of weak jaw closure and strong jaw opening is expected in MG. Test temporalis/pterygoid separately. Weak jaw opening with pterygoid weakness is rarely found in MG.
23. Fatigue of swallowing does occur in MG
24. Slurp test touted in May, 2010 Neurology podcast for children with MG that parents can do to test for weakness. fill 4 oz cup with water with a straw and have child slurp after finishing the drink. Time it, use patient as own control.
2. False positive tensilon tests occurred in LEMS< GBS, compressive cranial neuropathies and brain stem lesions (Seminars of Neurology 2003, author Pascuzzi).
3. Muscarinic effects (tearing, sweating,cramping, salivating and nausea) are common. Relative contraindications are cardiac arrythmias and asthma. Cardiac monitoring may not be universally required.
4. A neostigmine methylsulfate injection can be used in children with a longer onset and offset (latter is 30 minutes) but may be harder to interpret.
5. The ice pack test of placing the ice pack on for 2-5 minutes has reported high sensitivity and specificity but may be hard to tolerate for patients (Golnick AC et al. Opthalmology 1999 186:1282-6). The mean improvement with this test is 4.5 mm.
6. The rest test (close eyes for 3 minutes) results in a mean improvement of 2 mm of ptosis.
7. The sleep test (30 minutes) shows improvement in all Tensilon positive patients plus two others (out of 42 tested).
8. Lab tests of binding Ach receptors is positive in 50 % of OM patients (v. 90 % of MG patients overall); blocking antibodies add only another 1 percent sensitivity, and modulating antibodies actually do improve sensitivity slightly but also have more false positives. see Howard FJ et al. NY Acad Sci 1987; 505: 526-538).
9. False positive conditions with ACH receptor antibodies (again from Howard et al.) are: AI hepatitis, SLE, ALS, inflammatory neuropathies, LEMS, thyroid opthalmopathy, 1 degree relatives of MG patients, thymoma, RA, and patients taking penicillamine.
10. Striated muscle ab's as a marker for thymoma: they predict thymoma in patients with MG under 40 (80%) and thymoma in nonmyasthenics (positive in 25 % of those). False positives are seen in RA treated with penicillamine, LEMS, Bone marrow graft recipients, GVHD, and paraneoplastic disease (see Lennon, Neurol suppl 5, 1997 S23-27).
11. De Graefe's test 12. Mary Walker phenomenon-- inflation of cuff above normal systolic pressure causes fatigue. Deflation of the cuff causes exacerbation of MG in rest of the body
13. Fatigue-ability is the hallmark of MG. Test for with sustained upgaze test 30-60 sec (especially check medial rectus muscle> superior and lateral recti); sustained abduction of the arms (120 s); sustained elevation of the leg while lying supine (90 sec); repeated rising from a chair without using arms, up to 20 times, look for bfm's; counting aloud to 50.
14. The rare patient that presents with isolated respiratory involvement may have orthopnea, ie SOB while lying down.
15. Enhanced ptosis of contralateral side may occur with manual elevation of one ptotic lid
16. Unilateral frontal hypercontraction is a sign of weak lids.
17. Specific muscles to assess in suspected MG include eom's, oropharyngeal, facial, respiratory, axial and limb
18 Pseudo INO occurs when adducting eye does not adduct and abducting eye has nystagmus
19. Cover - uncover test can reveal weakness if done repeatedly.
20. Beware of holding target to fixate too close, will reveal a convergence abnormality rather than a true EOM abnormality.
21. Look for snarl with attempt to smile, inability to pucker to kiss
22. Pattern of weak jaw closure and strong jaw opening is expected in MG. Test temporalis/pterygoid separately. Weak jaw opening with pterygoid weakness is rarely found in MG.
23. Fatigue of swallowing does occur in MG
24. Slurp test touted in May, 2010 Neurology podcast for children with MG that parents can do to test for weakness. fill 4 oz cup with water with a straw and have child slurp after finishing the drink. Time it, use patient as own control.
Signs and symptoms of ocular myasthenia
1. Unilateral or bilateral ptosis, usually variable through the day, with diplopia
2. Chief complaint may be blurred vision if lid covers pupil and ptosis is not recognized.
3. Hyper-retraction of the less affected lid can cause a complaint of ocular irritation due to exposure.Hyperretraction is a compensatory mechanism with increased neuronal firing in less affected eye.
4. Dizziness, gait instability, blurring of "visual confusion" that improves with closing one eye
5. SPECIFIC SIGN OF MG: WHEN PTOTIC LID IS MANUALLY (passively) ELEVATED, THE CONTRALATERAL LID DROOPS
6. Cogan lid twitch sign: The patient looks down for 15 seconds, then rapidly up at the examiner's finger. The ptotic eyelid overshoots and is transiently higher than the contralateral lid then drops to its normal position. Its due to transient strengthening of the lid after resting the levator muscle.
7. Any pattern of EOM weakness
8. Dissociated gaze evoked nystagmus contralateral to the paretic eye.This is adaptive and due to increased pulses of innervation.
9. Orbicularis oculi weakness with ptosis is a strong suggestor of MG.
10. Peekaboo sign with gradual appearance of lagopthalmos after forceful lid closure of over a minute with fatigue and incomplete lid closure showing sclera, hence the name, is also seen in facial nerve disorders
11. Pupils are always normal, unlike botulism and IIIn palsy.
12. The "other" Babinski sign (aka "brow lift sign)-- "when orbicularis oculi contracts and the eye closes, the internal part of the frontalis contracts at the same time and the eyebrow raises during eye occlusion." This sign is helpfulin differentiating MG from blepharospasm.
2. Chief complaint may be blurred vision if lid covers pupil and ptosis is not recognized.
3. Hyper-retraction of the less affected lid can cause a complaint of ocular irritation due to exposure.Hyperretraction is a compensatory mechanism with increased neuronal firing in less affected eye.
4. Dizziness, gait instability, blurring of "visual confusion" that improves with closing one eye
5. SPECIFIC SIGN OF MG: WHEN PTOTIC LID IS MANUALLY (passively) ELEVATED, THE CONTRALATERAL LID DROOPS
6. Cogan lid twitch sign: The patient looks down for 15 seconds, then rapidly up at the examiner's finger. The ptotic eyelid overshoots and is transiently higher than the contralateral lid then drops to its normal position. Its due to transient strengthening of the lid after resting the levator muscle.
7. Any pattern of EOM weakness
8. Dissociated gaze evoked nystagmus contralateral to the paretic eye.This is adaptive and due to increased pulses of innervation.
9. Orbicularis oculi weakness with ptosis is a strong suggestor of MG.
10. Peekaboo sign with gradual appearance of lagopthalmos after forceful lid closure of over a minute with fatigue and incomplete lid closure showing sclera, hence the name, is also seen in facial nerve disorders
11. Pupils are always normal, unlike botulism and IIIn palsy.
12. The "other" Babinski sign (aka "brow lift sign)-- "when orbicularis oculi contracts and the eye closes, the internal part of the frontalis contracts at the same time and the eyebrow raises during eye occlusion." This sign is helpfulin differentiating MG from blepharospasm.
Differential diagnosis of ocular myasthenia
1.Any IV,VI, and partial IIInn palsies
2. Graves opthalmopathy (however, should not see ptosis, and may see lid retraction)
3. CPEO Chronic progressive external opthalmoplegia(get symmetric ptosis and EOM weakness, but unlike myasthenia, SACCADES ARE SLOW in CPEO
4. Oculopharyngeal dystrophy-- chronic, slowly progressive, family history present, bulbar mm are involved.
5. Glycogenosis type II -- ptosis is presenting feature often (Neurology 69 : 116 2007) with skeletal muscle weakness later. Muscle biopsy may be needed to show increased glycogen content and acid maltase deficiency,
6. Autoimmune encephalitis with diplopia: http://dementianotes.blogspot.com/2008/06/vgkc-autoantibodies-mimicking-cjd.html
2. Graves opthalmopathy (however, should not see ptosis, and may see lid retraction)
3. CPEO Chronic progressive external opthalmoplegia(get symmetric ptosis and EOM weakness, but unlike myasthenia, SACCADES ARE SLOW in CPEO
4. Oculopharyngeal dystrophy-- chronic, slowly progressive, family history present, bulbar mm are involved.
5. Glycogenosis type II -- ptosis is presenting feature often (Neurology 69 : 116 2007) with skeletal muscle weakness later. Muscle biopsy may be needed to show increased glycogen content and acid maltase deficiency,
6. Autoimmune encephalitis with diplopia: http://dementianotes.blogspot.com/2008/06/vgkc-autoantibodies-mimicking-cjd.html
Thursday, January 10, 2008
Seven agents approved for antimigraine prophylaxis
(list is in Lancet Neurology Dec 2007 editorial, suggests this applies to UK, in case some of the drugs sound unfamiliar). The seven are: methysergide, propanolol, timolol, pizotifen, flunarizine, valproate, and topiramate.
Monday, December 17, 2007
Corticosteroids for bacterial meningitis
editorial Greenwood BM. NEJM 2007; 357:2507-08 (editorial) and (same issue)
Mai NTH et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis pp. 2431-2440
and
Scarborough M et al. Corticosteroids for bacterial meningitis in adults in subSaharan Africa pp. 2441-2450.
The prologue is that meta-analysis in industrialized countries showed that dexamethasone given to children with Hemophilus B type b meningitis before antibiotics reduces sequelae, especially hearing loss (McIntyre PB et al. Jama 1997; 278:925-931. Studies in adults in ind. countries also show a benefit (NEJM 2002; Lancet Inf Dis 2004). A trial of 598 children in Malawi, about one third of whom were infected with the HIV virus, showed "convincing evidence of lack of benefit." Most African pediatricians have accepted the result (Lancet 2002). The study above (Scarborough et al.) of adults age greater than 16 with acute bacterial meningitis given dexamethasone 16 mg bid for four days with ceftriaxone showed no benefit of dexamethasone on any endpoint. In contrast, the study by Mai et al. in Vietnam of 435 persons odler than 14 with .4 mg/kg dexamethasone for 4 days of placebo before ceftriaxone, showed benefits in some analyses on death, hearing loss in treated group (if TB patients are excluded). Notable was the strikingly higher mortality in Africa v. Vietnam (54 v. 11%) possibly due to HIV infection, or a different infection (Str pn in Malawi S. suis in Vietnam). A South American study showed no benefit of dexamethasone, but benefit of glycerol (Clin Infect Dis 2007, author Peltola et al.). Editorial concludes the focus should be on vaccines although dexamethasone might be used in the developed world.
Mai NTH et al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis pp. 2431-2440
and
Scarborough M et al. Corticosteroids for bacterial meningitis in adults in subSaharan Africa pp. 2441-2450.
The prologue is that meta-analysis in industrialized countries showed that dexamethasone given to children with Hemophilus B type b meningitis before antibiotics reduces sequelae, especially hearing loss (McIntyre PB et al. Jama 1997; 278:925-931. Studies in adults in ind. countries also show a benefit (NEJM 2002; Lancet Inf Dis 2004). A trial of 598 children in Malawi, about one third of whom were infected with the HIV virus, showed "convincing evidence of lack of benefit." Most African pediatricians have accepted the result (Lancet 2002). The study above (Scarborough et al.) of adults age greater than 16 with acute bacterial meningitis given dexamethasone 16 mg bid for four days with ceftriaxone showed no benefit of dexamethasone on any endpoint. In contrast, the study by Mai et al. in Vietnam of 435 persons odler than 14 with .4 mg/kg dexamethasone for 4 days of placebo before ceftriaxone, showed benefits in some analyses on death, hearing loss in treated group (if TB patients are excluded). Notable was the strikingly higher mortality in Africa v. Vietnam (54 v. 11%) possibly due to HIV infection, or a different infection (Str pn in Malawi S. suis in Vietnam). A South American study showed no benefit of dexamethasone, but benefit of glycerol (Clin Infect Dis 2007, author Peltola et al.). Editorial concludes the focus should be on vaccines although dexamethasone might be used in the developed world.
Friday, December 07, 2007
Serotonin syndrome and its differential diagnosis and treatment
Boyer EW, Shannon M. Current Concepts. The Serotonin Syndrome. NEJM 2005; 352:1111-20.
General notes
1. The serotonin syndrome (SS) is not an idiopathic drug reaction but a predictable consequence of excess serotonergic drug stimulation of the CNS and peipheral receptors.
2. It has a spectrum of findings ranging from barely perceptible to lethal.
The classical triad is mental status changes, autonomic hyperactivity and neuromuscular abnormalities. Symptoms can include tremor, diarrhea, delirium, rigidity, shivering, mydriasis, tachycardia, hypertension, and hyperthermia. Inadvertent increase in the dose of a causative drug can provoke a dramatic deterioration.
Drugs and drug combinations include MAOI's, TCA's, SSRI's, opiates, OTC cough suppressants, antibiotics, weight reduction drugs, antiemetics, antimigraine drugs, drugs of abuse, herbal products, drugs that inhibit CYP2D6 and CYP3A4 systems, PAST use of fluoxetine (within 6 weeks), or illegal drug ecstasy. Most cases occur within minutes to hours after initiating a new medicine or increasing a dose. It does not resolve if offending drugs are still given.
Clinical notes: lower extremity hyprereflexia and clonus is much worse than the upper extremity. Horizontal ocular clonus and opsolclonus may occur. Mutism is not infrequent. Startle is increased, and repetitive head rotaton may occur. Patients may degenerate into frank shock. Diagnosis: Clonus (inducible, spontaneous or ocular) is the most important finding. The differential includes anticholinergic poisoning, malignant hyperthermia, and NMS which all are differentiated on clinical/historical grounds.
Anticholinergic patients have normal reflexes and "toxidrome" of mydriasis, agitated delirium, dry oral mucosa, hot dry skin, urine retention, absent bowel sounds (always present in SS). Malignant hyperthermia has increasing end tidal CO2 levels, ypertonicity, hyperthermia, and metabolic acidosis, within minutes of exposure to inhalational anesthesia. Skin exam shows mottling, cyanosis juxtaposed to bright red flushing. The skeletal muscles are rigid, and there is areflexia. NMS is an idiopathic reaction to DA agonists with slow onset, bradykinesia, lead pipe rigiditym hyperthermia, fluctuating consciousness and autonomic instability that evolves over hours to days (whereas SS has rapid onset and hyperkinesia).
Management involves removing offending drug, supportive care, control of ANS instability, and occassionally benzodiazepines. Moderately ill patients should aggressively correct CV and respiratory problems and receive 5H2a antagonists. Severely hyperthermic patients (41) should also be sedated, paralyzed and intubated. Benzodiazepines may be life saving. Physical restraints are not advised. The antidote is usually cyproheptadine, giving 12-32 mg over a 24 hour period (initial dose of 12 mg then 2 mg q 2 hours prn, given po, crushed in a Dobhoff). I-m thorazine can be used. Hypertension and tachycardia can be treated with short acting drugs such as esmolol and nitroprusside. Hyperthermia should be treated with nondepolarizing drugs such as vecuronium, NOT succinylcholine. Antipyretics are not indicated since fever is due to muscle activity and the hypothalamic set point is working OK. Propanolol is not indicated as it can cause hypotension and shock, and abolish reflex tachycardia. BCT and dantrolene are not useful (unlike NMS and malignant hyperthermia).
Cyproheptadine can be sedating but that is OK. Chlorpromazine can cause hypotension which is irrelevant.
General notes
1. The serotonin syndrome (SS) is not an idiopathic drug reaction but a predictable consequence of excess serotonergic drug stimulation of the CNS and peipheral receptors.
2. It has a spectrum of findings ranging from barely perceptible to lethal.
The classical triad is mental status changes, autonomic hyperactivity and neuromuscular abnormalities. Symptoms can include tremor, diarrhea, delirium, rigidity, shivering, mydriasis, tachycardia, hypertension, and hyperthermia. Inadvertent increase in the dose of a causative drug can provoke a dramatic deterioration.
Drugs and drug combinations include MAOI's, TCA's, SSRI's, opiates, OTC cough suppressants, antibiotics, weight reduction drugs, antiemetics, antimigraine drugs, drugs of abuse, herbal products, drugs that inhibit CYP2D6 and CYP3A4 systems, PAST use of fluoxetine (within 6 weeks), or illegal drug ecstasy. Most cases occur within minutes to hours after initiating a new medicine or increasing a dose. It does not resolve if offending drugs are still given.
Clinical notes: lower extremity hyprereflexia and clonus is much worse than the upper extremity. Horizontal ocular clonus and opsolclonus may occur. Mutism is not infrequent. Startle is increased, and repetitive head rotaton may occur. Patients may degenerate into frank shock. Diagnosis: Clonus (inducible, spontaneous or ocular) is the most important finding. The differential includes anticholinergic poisoning, malignant hyperthermia, and NMS which all are differentiated on clinical/historical grounds.
Anticholinergic patients have normal reflexes and "toxidrome" of mydriasis, agitated delirium, dry oral mucosa, hot dry skin, urine retention, absent bowel sounds (always present in SS). Malignant hyperthermia has increasing end tidal CO2 levels, ypertonicity, hyperthermia, and metabolic acidosis, within minutes of exposure to inhalational anesthesia. Skin exam shows mottling, cyanosis juxtaposed to bright red flushing. The skeletal muscles are rigid, and there is areflexia. NMS is an idiopathic reaction to DA agonists with slow onset, bradykinesia, lead pipe rigiditym hyperthermia, fluctuating consciousness and autonomic instability that evolves over hours to days (whereas SS has rapid onset and hyperkinesia).
Management involves removing offending drug, supportive care, control of ANS instability, and occassionally benzodiazepines. Moderately ill patients should aggressively correct CV and respiratory problems and receive 5H2a antagonists. Severely hyperthermic patients (41) should also be sedated, paralyzed and intubated. Benzodiazepines may be life saving. Physical restraints are not advised. The antidote is usually cyproheptadine, giving 12-32 mg over a 24 hour period (initial dose of 12 mg then 2 mg q 2 hours prn, given po, crushed in a Dobhoff). I-m thorazine can be used. Hypertension and tachycardia can be treated with short acting drugs such as esmolol and nitroprusside. Hyperthermia should be treated with nondepolarizing drugs such as vecuronium, NOT succinylcholine. Antipyretics are not indicated since fever is due to muscle activity and the hypothalamic set point is working OK. Propanolol is not indicated as it can cause hypotension and shock, and abolish reflex tachycardia. BCT and dantrolene are not useful (unlike NMS and malignant hyperthermia).
Cyproheptadine can be sedating but that is OK. Chlorpromazine can cause hypotension which is irrelevant.
Sunday, December 02, 2007
Therapy for nerve agent poisoning
Newmark, J. Therapy for nerve agent poisoning. Arch Neurol 2004; 61:649-652
Nerve agents include tabun (GA), sarin (GB), soman (GD), cyclosarin (GF) and VX. All evaporate and are gone within 24 hours, except VX which is oily and the only one which is persistent. VX is the most lethal substance known to man. The drugs were weaponized in Nazi Germany, used by Iraq against Iran in the Iraq-Iran war, and used in 2 subway attacks in Japan in 1994-5.
Clinical scenario-- in a shopping mall, you hear a "pop" and see smoke, your vision dims and nose runs severely. People may collapse, breathing heavily or seizing, with constricted pupils.
The mechanism is similar to organophosphate pesticides, although they are much less fat soluble and therefore more toxic. Theyinhibit AchE, acetylcholinesterase, producing a cholinergic crisis. Most exposures occur through the vapor route and act within seconds to minutes. The initial symptoms are miosis and rhinorhhea and salivation. Later, brochorrhea and bronchospasm occur. They are absorbed at the alveoli, and although they are not important clinically, the gold standard of diagnosis is RBC AChE. Circulating toxin first affects the GIT causing cramping, pain, nausea and defecation. It will affect the heart variably with unpredictable effects on BP and HR. They cause massive overstimulation of peripheral neuromuscular synapses witha progression from fasciculation to twitching that may be misinterpreted as a seizure. When ATP is depleted (a late finding) the patient will eventually have flaccid paralysis. Rapid CND cholinergic stimulation will cause LOC, seizures, inhibition of medullary respiratory center with central apnea. Death is due to respiratory failure (combined) due to bronchospasm, bronchorhhea, inadequate function of respiratorymuscles, and central apnea.
Liquid exposure has a longer slower onset and offset than vapor. Skin decontamination may not suffice if not done immediately, as nerve agent may be trapped subcutaneously and continue to penetrate.
Patients recovered frommild poisoning have a neurobehavioral syndrome including HA, personalitychange, depression, and higher order problemswith memory and reading. It may resemblePTSD or postanoxic encephalopathy. Chronic effects are few, with one report of a PN and a few of vestibular problems.
THERAPY:
Ventilatory support can be lifesaving even for someone in full arrest, if an antidote is given. Treatment has not changed since 1945 and includes an anticholinergic drug to counteract crisis, an oxime to reactivate inhibited AChE, and an AED to prevent seizures. In the field,atropine is used with i-m autoinjectorswith an initial therapy of 2,4,or 6 mg with retreatment every 5-10 minutes as needed. 0.5 or 1.0 mg ampules are available for children. In the hospital it may be given intravenously. Atropine binds to muscarinicreceptorsbut not nicotinic receptors, so twitching and dyscoordination will continue. The respiratory problems are life threatening and atropine saves lives,per the Iranian experience.
The fielded oxime is 2-pralidoximm chloride (2 PAM). The i-m dose is 600 mg per autoinjector. The upper limit is 2000 mg/hr due to the risk of sudden elevation of blood pressure. Oximes reactivate catalytic cholinesterase and simultaenously split nerve agent or organophosphate insectisides into harmless, rapidly metabolized fragments. After nerve agent binds AChE , the resultant complex spontaneously loses a side chain ("aging") rendering the remaining enzyme-inhibitor complex unable to be reactivated by oxime. Most nerve agents age slowly and the reaction can be ignores (sarin over hours, VX over days to weeks) but soman over two minutes. Once the complex has aged, the oximes are useless although not harmful to the patient.
The MARK 1 set (Meridian Medical Technologies, Columbia, MS) has a 2 mg atropine and 600 mg 2-PAM autoinjectors and is already approved by the FDA for the general use.
Standard AED's (antiepileptic drugs) are not useful for seizures due to nerve agents. Only benzodiazepines are effective. The military uses diazepam 10mg autoinjectors. Midazolam is the most effective, given i-v, in terms of speed of actions, low dose required, and broad spectrum. Epilepsy does not develop and chonic AED's are not advised.
The fourth drug available is pyridostigmine bromide, which may be useful if soldiers are concerned about a rapidly aging poison (soman) . Pyridostigmine will sequester a percentage of the patients excess AChE and render it unavailable to be irreversibly inhibited by a a nerve agent. Therefore a lethal dose becomes survivable with antidotes.
Care must be provided inthe field, not in the hospital (too late). Additional information is available at the chemical casualty division website at http://ccc.apgea.army.mil or the Army Medical Research Institute of Chemical Defense at (410) 436-3276.
Nerve agents include tabun (GA), sarin (GB), soman (GD), cyclosarin (GF) and VX. All evaporate and are gone within 24 hours, except VX which is oily and the only one which is persistent. VX is the most lethal substance known to man. The drugs were weaponized in Nazi Germany, used by Iraq against Iran in the Iraq-Iran war, and used in 2 subway attacks in Japan in 1994-5.
Clinical scenario-- in a shopping mall, you hear a "pop" and see smoke, your vision dims and nose runs severely. People may collapse, breathing heavily or seizing, with constricted pupils.
The mechanism is similar to organophosphate pesticides, although they are much less fat soluble and therefore more toxic. Theyinhibit AchE, acetylcholinesterase, producing a cholinergic crisis. Most exposures occur through the vapor route and act within seconds to minutes. The initial symptoms are miosis and rhinorhhea and salivation. Later, brochorrhea and bronchospasm occur. They are absorbed at the alveoli, and although they are not important clinically, the gold standard of diagnosis is RBC AChE. Circulating toxin first affects the GIT causing cramping, pain, nausea and defecation. It will affect the heart variably with unpredictable effects on BP and HR. They cause massive overstimulation of peripheral neuromuscular synapses witha progression from fasciculation to twitching that may be misinterpreted as a seizure. When ATP is depleted (a late finding) the patient will eventually have flaccid paralysis. Rapid CND cholinergic stimulation will cause LOC, seizures, inhibition of medullary respiratory center with central apnea. Death is due to respiratory failure (combined) due to bronchospasm, bronchorhhea, inadequate function of respiratorymuscles, and central apnea.
Liquid exposure has a longer slower onset and offset than vapor. Skin decontamination may not suffice if not done immediately, as nerve agent may be trapped subcutaneously and continue to penetrate.
Patients recovered frommild poisoning have a neurobehavioral syndrome including HA, personalitychange, depression, and higher order problemswith memory and reading. It may resemblePTSD or postanoxic encephalopathy. Chronic effects are few, with one report of a PN and a few of vestibular problems.
THERAPY:
Ventilatory support can be lifesaving even for someone in full arrest, if an antidote is given. Treatment has not changed since 1945 and includes an anticholinergic drug to counteract crisis, an oxime to reactivate inhibited AChE, and an AED to prevent seizures. In the field,atropine is used with i-m autoinjectorswith an initial therapy of 2,4,or 6 mg with retreatment every 5-10 minutes as needed. 0.5 or 1.0 mg ampules are available for children. In the hospital it may be given intravenously. Atropine binds to muscarinicreceptorsbut not nicotinic receptors, so twitching and dyscoordination will continue. The respiratory problems are life threatening and atropine saves lives,per the Iranian experience.
The fielded oxime is 2-pralidoximm chloride (2 PAM). The i-m dose is 600 mg per autoinjector. The upper limit is 2000 mg/hr due to the risk of sudden elevation of blood pressure. Oximes reactivate catalytic cholinesterase and simultaenously split nerve agent or organophosphate insectisides into harmless, rapidly metabolized fragments. After nerve agent binds AChE , the resultant complex spontaneously loses a side chain ("aging") rendering the remaining enzyme-inhibitor complex unable to be reactivated by oxime. Most nerve agents age slowly and the reaction can be ignores (sarin over hours, VX over days to weeks) but soman over two minutes. Once the complex has aged, the oximes are useless although not harmful to the patient.
The MARK 1 set (Meridian Medical Technologies, Columbia, MS) has a 2 mg atropine and 600 mg 2-PAM autoinjectors and is already approved by the FDA for the general use.
Standard AED's (antiepileptic drugs) are not useful for seizures due to nerve agents. Only benzodiazepines are effective. The military uses diazepam 10mg autoinjectors. Midazolam is the most effective, given i-v, in terms of speed of actions, low dose required, and broad spectrum. Epilepsy does not develop and chonic AED's are not advised.
The fourth drug available is pyridostigmine bromide, which may be useful if soldiers are concerned about a rapidly aging poison (soman) . Pyridostigmine will sequester a percentage of the patients excess AChE and render it unavailable to be irreversibly inhibited by a a nerve agent. Therefore a lethal dose becomes survivable with antidotes.
Care must be provided inthe field, not in the hospital (too late). Additional information is available at the chemical casualty division website at http://ccc.apgea.army.mil or the Army Medical Research Institute of Chemical Defense at (410) 436-3276.
Multiple auras: clinical significanceand pathophysiology
Widdiss-Walsh P, Kotagel P et al. Multiple auras: clinical significance and pathophysiology. Neurology 2007; 69:755-761.
Ninety percent of those with two aura types and 100 % of those with three aura types have right hemisphere localization of their seizures. Some examples were rising epigastric sensation with a simultaneous unpleasant odor or visual field distortion. Multiple auras previously are considered commoner in in patients "alien tissue" (v. mesial temporal sclerosis).
Ninety percent of those with two aura types and 100 % of those with three aura types have right hemisphere localization of their seizures. Some examples were rising epigastric sensation with a simultaneous unpleasant odor or visual field distortion. Multiple auras previously are considered commoner in in patients "alien tissue" (v. mesial temporal sclerosis).
Thursday, November 15, 2007
Miscellaneous drug facts most people do not know
Antiepileptic drug random facts
1. Phenytoin (more misc. on than we already new)- a. increases HDL levels.
b. Formula to adjust PTN dose. In zero order kinetics, a fixed AMOUNT not percentage of phenytoin is metabolized. Vd= .7 L/kg Loading dose = (Vd) x (desired change in concentration) so eg. raise the level from 5 to 18 in a 100 kg man would mean Vd=70L, loading dose = 70 x 13= 910 mg. Phenytoin is saturably absorbed in duodenum and affected by food and by antacids
2. Cerebyx has the same Tmax as Dilantin due to time required to cleave the "fos" of fos phenytoin. Cerebyx also has some cardiac toxicity despite the absent phenylene glycol adjuvant. Infusion can be faster than Dilantin but not more than 150 mg/min. It prevents the purple glove but not time to treat SE.
3. PTN, CBZ and PB block efficacy of some chemotherapeutic agents (see post)http://neurologyminutiae.blogspot.com/2007/11/drug-interactionsenzyme-inducers-and.html
4. Depakote
a. may be useful in brain tumor treatment irrespective of AED effect (see post) http://neurologyminutiae.blogspot.com/2007/07/valproic-acid-and-brain-tumors.html
b. Depakote is highly bound but not to albumen; and free levels are difficult to measure. Its level rises in cirrhosis. Its path is 80 % direct glucuronidation, 17 % is in same oxidative path as free fatty acids and enters the carnitine shuffle, leading to 4, en VPA. Many ICU patients are carnitine deficient which shunts VPA to toxic metabolism so give these patients carnitine 25 mg/kg png over six hours leads to less NH4+.
5. Vimpat can cause angioedema
DRUGS FOR DEMENTIA
1. Rivastigmine patches can be left on for more than 24 hours as they have a 24 hour half life (in effect, patients are throwing away active drug). Wearing multiple patches, duly labelled, is one way to dispense a higher dose, usually with limited adverse effects
2. Memantine has histamine blocking properties and its use may limit GI adverse events of individuals taking rivastigmine or other drugs.
3. Cholinesterase inhibitors inhibit metabolism of suxamethonium, prolonging neuromuscular blockade
OTHER
1. Prazosin is highly effective for post-traumatic stress disorder
2. Levodopa-carbidopa and gabapentin are two rare drugs that are gastric absorbed and in fact compete with each other. Better to stop the gabapentin in Parkinson patients.3. Protease inhibitors potentiate toxicity of GHB, so HIV patients attending circuit parties are at extra high risk of coma and death.
4. Drug rash to Sinemet is due to yellow dye not levodopa carbidopa (see post) http://neurologyminutiae.blogspot.com/2007/04/rash-to-yellow-dye-in-levodopa.html
5. Natalizumab also blocks trafficking of B cells into CNS
6. . Atorvastatin, even brief exposure, causes a marked decrease in blood Co Q 10 concentration (shares the synthetic pathway of cholesterol). Primary CoQ10 deficiency causes mitochondrial encephalomyopathy with recurrent myoglobinuria; this may pertain to AE's of atorvastatin. Also, CoQ10 is an excellent free radical scavenger and the effects on degenerative disease are not known. Rundek et al,. Arch Neurol 2004; 61: 889-892.
1. Phenytoin (more misc. on than we already new)- a. increases HDL levels.
b. Formula to adjust PTN dose. In zero order kinetics, a fixed AMOUNT not percentage of phenytoin is metabolized. Vd= .7 L/kg Loading dose = (Vd) x (desired change in concentration) so eg. raise the level from 5 to 18 in a 100 kg man would mean Vd=70L, loading dose = 70 x 13= 910 mg. Phenytoin is saturably absorbed in duodenum and affected by food and by antacids
2. Cerebyx has the same Tmax as Dilantin due to time required to cleave the "fos" of fos phenytoin. Cerebyx also has some cardiac toxicity despite the absent phenylene glycol adjuvant. Infusion can be faster than Dilantin but not more than 150 mg/min. It prevents the purple glove but not time to treat SE.
3. PTN, CBZ and PB block efficacy of some chemotherapeutic agents (see post)http://neurologyminutiae.blogspot.com/2007/11/drug-interactionsenzyme-inducers-and.html
4. Depakote
a. may be useful in brain tumor treatment irrespective of AED effect (see post) http://neurologyminutiae.blogspot.com/2007/07/valproic-acid-and-brain-tumors.html
b. Depakote is highly bound but not to albumen; and free levels are difficult to measure. Its level rises in cirrhosis. Its path is 80 % direct glucuronidation, 17 % is in same oxidative path as free fatty acids and enters the carnitine shuffle, leading to 4, en VPA. Many ICU patients are carnitine deficient which shunts VPA to toxic metabolism so give these patients carnitine 25 mg/kg png over six hours leads to less NH4+.
5. Vimpat can cause angioedema
DRUGS FOR DEMENTIA
1. Rivastigmine patches can be left on for more than 24 hours as they have a 24 hour half life (in effect, patients are throwing away active drug). Wearing multiple patches, duly labelled, is one way to dispense a higher dose, usually with limited adverse effects
2. Memantine has histamine blocking properties and its use may limit GI adverse events of individuals taking rivastigmine or other drugs.
3. Cholinesterase inhibitors inhibit metabolism of suxamethonium, prolonging neuromuscular blockade
OTHER
1. Prazosin is highly effective for post-traumatic stress disorder
2. Levodopa-carbidopa and gabapentin are two rare drugs that are gastric absorbed and in fact compete with each other. Better to stop the gabapentin in Parkinson patients.3. Protease inhibitors potentiate toxicity of GHB, so HIV patients attending circuit parties are at extra high risk of coma and death.
4. Drug rash to Sinemet is due to yellow dye not levodopa carbidopa (see post) http://neurologyminutiae.blogspot.com/2007/04/rash-to-yellow-dye-in-levodopa.html
5. Natalizumab also blocks trafficking of B cells into CNS
6. . Atorvastatin, even brief exposure, causes a marked decrease in blood Co Q 10 concentration (shares the synthetic pathway of cholesterol). Primary CoQ10 deficiency causes mitochondrial encephalomyopathy with recurrent myoglobinuria; this may pertain to AE's of atorvastatin. Also, CoQ10 is an excellent free radical scavenger and the effects on degenerative disease are not known. Rundek et al,. Arch Neurol 2004; 61: 889-892.
A 16 year old girl with progressive weakness of the let leg
Hahn AF, Mauermann ML, Dyck PJB, Keegan BM/ CPC. Neurology2007;69:84-90. Insidious onset of left LE weakness started at age 13, progressing to complete footdrop. She had normal sensation and reflexes. She had gobs of negative tests. Motor exam showed mild weakness in posterior tibialis and hamstring, severe weakness in the tibialis anterior, to extensors and peroneii, and normal gastrocnemius and toe flexors. She had mild pes cavus. EMG showed normal left tibial nerve conductions, left peroneal motor and surals were absent or severely abnormal. Needle testing showed marked denervation distal to the short head of the biceps. QST's were normal. MRI showed mild increase int he size and signal intensity of the left peroneal nerve in the peroneal division only. Anatomic localization implicated the common peroneal nerve or divisional sciatic nerve. Discussant notes that the tibial and peroneal divisions of the sciatic nerve are segregated as the sciatic nerve passes from the sciatic notch, so a sciatic lesion can mimic a peroneal neuropathy. In such cases needle EMG of the short head of the biceps is crucial. MRI neuronography showed enlarged peroneal nerve ipsilaterally. The diagnosis on biopsy of the nerve was intraneural perineuroma (aka localized hypertrophic mononeuropathy). It presents as a painless motor mononeuropathy in younger patients in a variety of nerves (posterior interosseous, radial ulnar). MRI differentiates from fibrolipomatous hamartoma, but not intraneural ganglion cysts. Intraoperatively, internal neurolysis can suggest the diagnosis also. Unlike true onion bulbs, which are S100 positive, these are S100 negative and EMA positive.
Friday, November 09, 2007
SSPE
Cole AJ, Henson JW, Roehrl MHA et al. Case 24-1007: A 20 year old pregnant woman with altered mental status. NEJM 2007; 357: 589-600.
Case showed a young pregnant woman with clinical presentation of aseptic meningitis: confusion, lymphocytic pleocytosis in CSF, FIRDA on EEG, ,MRI showing dysfunction in a non hSVE pattern affecting internal capsule and cerebellar outflow tract, gads of negative tests. MRI affected left temporal lobe and pons. The patient had chorea which brought up Strep infection and Syndenham's chorea but ASO was only minimally positive and ACL's were negative. There was marked increase in CSF IgG levels, IgG index and oligoclonal bands. According to Dr. Cole, that narrowed it to syphilis, chronic rubella encephalitis, and SSPE.
Measles causes 3 different CNS diseases: postinfectious encephalomyelitis, subacute measles encephalitis, and SSPE. SSPE occurs 7-10 years after infection with behavioral changes, headache, adventitious movements, and sometimes seizures. Myoclonic jerks and PLEDs on EEG may occur. It may occur from childhood until fifth decade of life. It persists in places where measles vaccination remains uncommon. It is more common if measles occurred at age < 2 years, and may be more common in pregnancy. The diagnostic test is measles specific CSF IgG antibody index compared to serum. Iit maybe compared to a control infection such as mumps. This patients was treated with interferon and pranobex for eight weeks, delivered a healthy baby and then expired. SSPE is considered almost always a progressive disease. This patient may have shown signs in a prior pregnancy of a movement disorder.
Case showed a young pregnant woman with clinical presentation of aseptic meningitis: confusion, lymphocytic pleocytosis in CSF, FIRDA on EEG, ,MRI showing dysfunction in a non hSVE pattern affecting internal capsule and cerebellar outflow tract, gads of negative tests. MRI affected left temporal lobe and pons. The patient had chorea which brought up Strep infection and Syndenham's chorea but ASO was only minimally positive and ACL's were negative. There was marked increase in CSF IgG levels, IgG index and oligoclonal bands. According to Dr. Cole, that narrowed it to syphilis, chronic rubella encephalitis, and SSPE.
Measles causes 3 different CNS diseases: postinfectious encephalomyelitis, subacute measles encephalitis, and SSPE. SSPE occurs 7-10 years after infection with behavioral changes, headache, adventitious movements, and sometimes seizures. Myoclonic jerks and PLEDs on EEG may occur. It may occur from childhood until fifth decade of life. It persists in places where measles vaccination remains uncommon. It is more common if measles occurred at age < 2 years, and may be more common in pregnancy. The diagnostic test is measles specific CSF IgG antibody index compared to serum. Iit maybe compared to a control infection such as mumps. This patients was treated with interferon and pranobex for eight weeks, delivered a healthy baby and then expired. SSPE is considered almost always a progressive disease. This patient may have shown signs in a prior pregnancy of a movement disorder.
Saturday, November 03, 2007
Drug interactions,enzyme inducers and anticancer
PTN, CBZ and PB induce cytochome P450 and reduces bioavailability of many chemotherapeutic drugs and warfarin. The former include camptothecins (topotecan and irinotecan) and taxanes (paclitaxol).
Mayo Clin Prcds combination of risperidol and gingko caused priaprism
Mayo Clin Prcds combination of risperidol and gingko caused priaprism
Friday, July 06, 2007
Valproic acid and brain tumors
Besides its antiepileptic effects, valproic acid promotes differentiation of neurons into mature cell liens and inhibits proliferation of neuroectodermal lines. This has led to the use of valproic acid in pediatric patients who are s/p chemotherapy and radiation therapy for malignant glioma (Driever etal. al Klin Ped 1999; 21:323-8). Valproic acide also inhibits histone deacetylases, as do topamax and one of the metabolites of levitiracetam (PBA).
MGMT gene silencing and temozolamide in GBM
Hegi et al. NEJM 2005; 352:997-1003
Epigenetic gene silencing of the MGMT (06 methylguanine DNA methyltransferase) DNA repair gene by promoter methylation compromises DNA repair and is associated with longer survival in GBM patients receiving chemotherapy. This was also found to be true in radiotherapy; patietns with a methylated MGMT promoter had a survival benefit.
Epigenetic gene silencing of the MGMT (06 methylguanine DNA methyltransferase) DNA repair gene by promoter methylation compromises DNA repair and is associated with longer survival in GBM patients receiving chemotherapy. This was also found to be true in radiotherapy; patietns with a methylated MGMT promoter had a survival benefit.
Oligodendroglioma: towards definition and treatment
Reifenberger G, Louis DN. Oligodendroglioma: towards molecular definitions in diagnostic neurooncology. Journal of Neuropathology and Experimental Neurology. 2003; 62:111-126.
Since 1988 the treatment options have differed for different types of gliomas. Recurrent anaplastic astrocytomas sometimes respond dramatically to PCV (procarbazine, lomustine and vincristine). Since 1990 the same is true for newly diagnosed analplastic oligodendrogliomas. The response may be durable and may also occur with temozolomide, an oral agent.
Diagnostic markers such as Olig1 and Olig2 are not reliable. Microtubule associated protein (MAP2) is not specific although it is sensitive. In 1998 Cairncross reported response to chemo is strongly related to allelic losses on 1p or 19q in resected tumor tissue. The correspond to WHO grade II tumors. Testing is performed at a few specialized labs and is not considered routine. At MGH LOH 1p and 19q testing costs $800. In another study, Kim and Kim (Acta Neuropath 2005) found two light microscopy histological features, tumor cellularity and perinuclear halo were associated with the two markers above.
Since 1988 the treatment options have differed for different types of gliomas. Recurrent anaplastic astrocytomas sometimes respond dramatically to PCV (procarbazine, lomustine and vincristine). Since 1990 the same is true for newly diagnosed analplastic oligodendrogliomas. The response may be durable and may also occur with temozolomide, an oral agent.
Diagnostic markers such as Olig1 and Olig2 are not reliable. Microtubule associated protein (MAP2) is not specific although it is sensitive. In 1998 Cairncross reported response to chemo is strongly related to allelic losses on 1p or 19q in resected tumor tissue. The correspond to WHO grade II tumors. Testing is performed at a few specialized labs and is not considered routine. At MGH LOH 1p and 19q testing costs $800. In another study, Kim and Kim (Acta Neuropath 2005) found two light microscopy histological features, tumor cellularity and perinuclear halo were associated with the two markers above.
Sunday, June 17, 2007
Saturday, May 19, 2007
Listeria encephalitis
case discussion in Reviews in Neurological Diseases. The typical presentation is rhombencephalitis with a fever. It affects often pons and medulla in middle aged adults who are not immunocompromised. The prodrome is low grade fever, headache, encephalitis, vomiting and malaise lasting up to two weeks, followed by abrupt onset of cranial nerve palsies and encephalopathy. The cranial nerve palsies are often strikingly assymetric. The most common findings are dysphagia, dysphonia, dysarthria, facial weakness, diplopia and nystagmus. INO is described in those with a pontine abscess. Urinary retention is described due to involvement of Barrington's nucleus. CSF gram stain is often negative and diagnosis may require serologic tests. There is 75 % chance of survival if treatment is initiated promptly.
Saturday, May 05, 2007
Brain MRI findings in mitochondrial cytopathies
Barragan-Campos H et al. Arch Neurol 2005; 62:737-742. 21 patients were described, including 7 with CPEO, 7 with Kearns-Sayre, 6 with mitochondrial neurogastrointestinal encephalopathy, and 1 with myoclonic epilepsy with ragged red fiber myopathy. MRi showed widespread white matter hyperintensity in 90 %, supracortical atrophy in 18, cerebellar atrophy in 13 ABSENT BASAL GANGLIA HYPERINTENSITY CORRELATED WITH KEARNS SAYRE AND SUPRATENTORIAL ATROPHY WITH mitochondrial neurogastrointestinal encephalopathy.
Clinical criteria: CPEO-- ext opthalmopledia, proximal myopathy and RRF. KS-- ext opthalmoplegia, heart block, pigmentary retinopathy, cerebellar ataxia, eolevated CSF protein (the latter two were "optional"). MNGIE-- leukoencephalopathy, CPEO, PN, chronic intestinal pseudoobstruction MERRF- myoclonic epilepsy, myoclonic ataxia, dementia, and RRF.
Clinical criteria: CPEO-- ext opthalmopledia, proximal myopathy and RRF. KS-- ext opthalmoplegia, heart block, pigmentary retinopathy, cerebellar ataxia, eolevated CSF protein (the latter two were "optional"). MNGIE-- leukoencephalopathy, CPEO, PN, chronic intestinal pseudoobstruction MERRF- myoclonic epilepsy, myoclonic ataxia, dementia, and RRF.
Wednesday, May 02, 2007
Cryptococcus/fungals/meningoencephalitis pearls (Dr Perfect AAN 2007 lecture)
1. Cryptococcus neoformans serotype A and D (grubii and neofomans) and serotype B and C (Cr. gattii) are major serotypes. Gattii affects more normal hosts and has more torulomas.
2. Consider IRIS (immune reconstition syndrome) in HIV patients starting HAART or with any CHANGE in immunosuppressive regiment. If patient seems to be getting worse in spite of treatment, this may be one of the few times to pay attention to the Crypto antigen titer. If it is dropping the patient may have IRIS and may not be failing therapy.
3. Don't put a shunt in until the patient is already on treatment-- you'll just have to replace it later. Increased ICP can occur on presentation chronic and indolent, acutely during early therapy, or classic hydrocephalus with therapy. Consider increased ICP if frequent and severe headaches, pappilledema, hearing loss, or pathologic reflexes present. Consider repeat LP's as a treatment modality. Shunts don't work often in comatose patients.
4. Indications for surgery include diagnostic biopsy, toruloma greater than 3 mm, zygomycetes and infarcted tissue, phaeohyphomycosis, shunt placement.
5. Diagnosis of other fungi clues: neutrophilic meningitis (aspergillus, scedosporium, blastomyces, zygomycetes), large volume CSF cultures (Blasto/histo/coccidio). Histoplasmosis antigen, sporotrix CSF antibodies, cocciiodes CFA, aspergillus galactomannan.
6. Wangiella (Exophiala) dermatitidis meningitis occurs due to injectable steroids that are contaminated, with a 1-11 month incubation period. Therapy with voriconazole.
7. Hyalohyphomycosis-- occurs in near fresh water drownings, due to steroids, and diabetes, usually from sinus disease, causes abscesses, surgery is critical for diagnosis and debulking.
8. Drug resistance is rare but it occurs.
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