Depalma RG, Burris DG, Champion HR et al. NEJM 2005; 352: 1335-1342.
1. Blast wave has a shock wave of high pressure followed by a blast wind of air motion. The physics are nonlinear and complex, and damage decreases exponentially with distance from the source. Inddors, reflections and reverberations produce additional unpredictable damage. Enhanced blast explosive devices outdoors can be more damaging. The pressure effects damages organs at air-fluid interfaces, and the wind propels fragments and people causing penetrating or blunt injuries.
2. There are 4 types of blast inuries: primary (effect of pressure), secondary (effect of projectiles), tertiary (effects of wind) and quaternary (burns, asphyxia and exposure to toxic inhalants).
Primary blast injuries-- barotrauma-- at air fluid interfaces are due to interaction of a high frequency stress wave and a lower frequency shear wave. Most important are rupture of the tympanic membranes, pulmonary damage and air emboli (including to brian and spinal cord) rupture of the hollow viscera. The eardrum can rupture with an increase of pressure as small as 5 psi above ATM (about 1/3 atm or 250 mm Hg). Deafness, tinnitus and vertigo results. Pressure gradients of 56-76 psi (3.9-5.2 atm) are needed to damage other organs. Occassionally people have other damage without eardrum damage. Lung injuries include bihilar butterfly pattern on CXR, PTX, hemothorax, pneumomediastinum, and and subcutaneous emphysema. Frothing at mouth (pulmonary edema) with whiteout CXR has a grave prognosis. Body armor protects against projectiles but not against barotrauma including pulmonary barotrauma.
Systemic gas emboli affecting the brain or spinal cord must be diferentiated from head trauma and concussion.
Colonic rupture or occassionally other organ rupture or infarction may be initially difficult to detect and are associated with proximity to blast center. Barotrauma to the eye can cause globe rupture, serous retinitis or hyphema.
Secondary blast injuries-- penetrating fragments are the leading cause of death and injury in attacks, except for major building collapse.
tertiary injuries-- includes crush injuries (buildings), leading to oliguric renal failure; compartment syndromes, characterized by pain out of proportion to the injury. In an earthquake in Japan (1995) mortality increased in patients trapped more than 24 hours due to tertiary injuries.
Quaternary-- includes everything else
Saturday, February 09, 2008
Myositis with fever and tick borne illnesses
1. Toxoplasmosis causes myosits and hepatitis but usually not high fevers or DIC
2. Lyme disease from deer tick peaks in spring when nymphal forms are feeding. The bites look like blood blisters and may be unnoticed. It occurs in the upper midwest as well as New England.
3. Deer tick also causes human granulocytic ehrlichosis and babesiosis. The former is caused by the lone star tick which is seen in the southern US and not New England. Babesiosis usually causes anemia, and is worse among patients who are old or immunosuppressed or asplenic.
4. The dog tick or wood tick transmits Rocky Mountain spotted fever and tularemia. RMSF causes a vasculitis with headache and a rash. Tick borne tularemia causes an ulceroglandular disease then an eschar and lymphadenopathy.
5. The ornithodoros tick transmits relapsing fever but again not in New England.
Ehrlichosis has a 7-10 day incubation period, multiorgan involvement, HA, myalgias and malaise, with mortality of 1-10 percent. Patients may have (less than 50 %) n/v/d/cough/stiff neck and mental status changes. They may have pancytopenia,a left shift, lymphocytosis, and elevated transaminases. It DOES NOT RESPOND TO MOST ANTIBIOTICS OTHER THAN DOXYCYCLINE
2. Lyme disease from deer tick peaks in spring when nymphal forms are feeding. The bites look like blood blisters and may be unnoticed. It occurs in the upper midwest as well as New England.
3. Deer tick also causes human granulocytic ehrlichosis and babesiosis. The former is caused by the lone star tick which is seen in the southern US and not New England. Babesiosis usually causes anemia, and is worse among patients who are old or immunosuppressed or asplenic.
4. The dog tick or wood tick transmits Rocky Mountain spotted fever and tularemia. RMSF causes a vasculitis with headache and a rash. Tick borne tularemia causes an ulceroglandular disease then an eschar and lymphadenopathy.
5. The ornithodoros tick transmits relapsing fever but again not in New England.
Ehrlichosis has a 7-10 day incubation period, multiorgan involvement, HA, myalgias and malaise, with mortality of 1-10 percent. Patients may have (less than 50 %) n/v/d/cough/stiff neck and mental status changes. They may have pancytopenia,a left shift, lymphocytosis, and elevated transaminases. It DOES NOT RESPOND TO MOST ANTIBIOTICS OTHER THAN DOXYCYCLINE
Combination therapy for neuropathic pain
Gilron I,Bailey JM, et al. Morphone, gabapentin or their combination fo rneuropathic pain. NEJM 2005; 352: 1324-1334 (article) and editorial Raja SN, Haythornthwaite JA. Combination therapy for neuropathic pain-- which drugs, which combination, which patients: NEJM 2005; 352: 1373-5.
In the article, authors study 57 patients with diabetic neuropathy or postherpetic neuralgia, and found that the combination titrated concurrently achieved better analgesia at lower doses of each drug than either one as a single agent.
In clinical management, expert panels suggest that when relief with gabapentin is incomplete, to add a second agent, which may be an opiod.
In the article, authors study 57 patients with diabetic neuropathy or postherpetic neuralgia, and found that the combination titrated concurrently achieved better analgesia at lower doses of each drug than either one as a single agent.
In clinical management, expert panels suggest that when relief with gabapentin is incomplete, to add a second agent, which may be an opiod.
Postpartum headache
Positional HA described, CT shows an air bubble, headache treated successfully with a blood patch.
Mimic syndromes in sporadic cases of progressive spinal muscular atrophy
Visser J, van den Berg-Vos RM, Franssen H et al. Neurology 2002; 58:1593-1596.
This is a progressive disease of lower motor neurons, aka progressive muscular atrophy, progressive spinal muscular atrophy, and others. Often patients develop UMN signs and qualify for a diagnosis of ALS and these patients are often considered part of the ALS spectrum. The study in the Netherlands was of 89 patients, 17 of whom had other diagnoses in the end. Patients were specifically excluded if they had objective sensory signs, history of diseases that could mimic PMA (spinal radiculopathy, poliomyelitis, diabetic amyotrophy), familyhistoryof SMA, or upper motor neuron signs. 7 patients ultimately met criteria for MMN, 2 with CIDP, 1 limb-gircle dystrophy, 1 inflammatory myopathy, others idiopathic chronic neuropathy, brachial plexopathy, syringomyelia and myopathy. One patient a HNP that recovered, and one had slowly progressive ALS.
This is a progressive disease of lower motor neurons, aka progressive muscular atrophy, progressive spinal muscular atrophy, and others. Often patients develop UMN signs and qualify for a diagnosis of ALS and these patients are often considered part of the ALS spectrum. The study in the Netherlands was of 89 patients, 17 of whom had other diagnoses in the end. Patients were specifically excluded if they had objective sensory signs, history of diseases that could mimic PMA (spinal radiculopathy, poliomyelitis, diabetic amyotrophy), familyhistoryof SMA, or upper motor neuron signs. 7 patients ultimately met criteria for MMN, 2 with CIDP, 1 limb-gircle dystrophy, 1 inflammatory myopathy, others idiopathic chronic neuropathy, brachial plexopathy, syringomyelia and myopathy. One patient a HNP that recovered, and one had slowly progressive ALS.
Ross syndrome plus: beyond Horner, Holmes-Adie and Harlequin
Shin RK, Galetta SL, Ting TY. Neurology2000; 55: 1841-1846.
Ross syndrome is defined by the triad of tonic pupils, hyporeflexia, and segmental anhidrosis. Holmes-Adie is tonic pupils and areflexia, and harlequin is segmental anhidrosis without ocular changes.
Ross syndrome is defined by the triad of tonic pupils, hyporeflexia, and segmental anhidrosis. Holmes-Adie is tonic pupils and areflexia, and harlequin is segmental anhidrosis without ocular changes.
Fatal initial adult-onset presentation of urea cycle defect
Lien J, Nyhan WL, Barshop BA. Arch Neurol 2007; 64:1777-1779.
Ornithine transcarbamylase (OTC) deficiency more commonly occurs in neonates,but can occur in adults. It leads to elevations in ammonia, encephalopathy and coma due to cerebral edema, and death. It is treatable (if diagnosed) with hemodialysis, intravenous arginine, and sodium benzoate/phenylacetate.
In this case report, a 20 yo presented to UCSD with metabolic disease 7 months after her father sudenly became hyperammonemic and died at 52. She had NO other family or personal medical history of prior episodes, and exam was normal. Her father awaoke 8 days after surgery for a throat polyp confused and combatative, developed seizures and had ammonia of 4202. He had cerebral edema and punctate pontine hemorrhages at autopsy.
The daughter later became pregnant with twins, and amniocentesis showed a mutation in both fetuses. She was then admitted given oral citrulline and a low protein diet. The first baby was delivered at 33 weeks vaginally, subsequently intubated, treated with a low protein diet, iv arginine and oral citrulline one he tolerated enteral feedings and did well.
The second baby also had perinatal problems but was treated as above and did well, both discharged at 6 weeks on low protein diets and citrulline and remained healthy.
The differential of the high ammonia in the father included disorders of fatty acid oxidation of organic acidemias. Plasma amino acid levels were normal ( including glutamine, alanine, citrulline, arginine) and urine for organic acids were normal (Orotic acid, uracil). PCR showed a change in codon 208 of exon 6 from GCA to ACA, as happened in amniotic fluid of his grandsons.
These patients are relatively easy to treat once diagnosed, and no longer are the province of pediatric neurologists alone. PEARL-- female heterozygotes are often asymptomatic or minimally symptomatic.
Differential- of headache progressing tohyperammonemic coma can occur with any disorder of the urea cycle. Hyperammonemic citrin deficiency (citrullinemia type II) usually presents in adulthood, sometimes with sometimes without intrahepatic cholestasis and can result in death. Hyperammonemic coma can occur in hyperornithemia, as well. There are over 300 mutations known. Plasma amino acids can show elevated glutamine, alanine or aspartic acid. Citrulline may be low. Organic acids in the urine can show orotic acid or uracil high. Enzyme assay requires liver biopsy but 80 % of diagnoses are made by sequence analysis at this point.
Ornithine transcarbamylase (OTC) deficiency more commonly occurs in neonates,but can occur in adults. It leads to elevations in ammonia, encephalopathy and coma due to cerebral edema, and death. It is treatable (if diagnosed) with hemodialysis, intravenous arginine, and sodium benzoate/phenylacetate.
In this case report, a 20 yo presented to UCSD with metabolic disease 7 months after her father sudenly became hyperammonemic and died at 52. She had NO other family or personal medical history of prior episodes, and exam was normal. Her father awaoke 8 days after surgery for a throat polyp confused and combatative, developed seizures and had ammonia of 4202. He had cerebral edema and punctate pontine hemorrhages at autopsy.
The daughter later became pregnant with twins, and amniocentesis showed a mutation in both fetuses. She was then admitted given oral citrulline and a low protein diet. The first baby was delivered at 33 weeks vaginally, subsequently intubated, treated with a low protein diet, iv arginine and oral citrulline one he tolerated enteral feedings and did well.
The second baby also had perinatal problems but was treated as above and did well, both discharged at 6 weeks on low protein diets and citrulline and remained healthy.
The differential of the high ammonia in the father included disorders of fatty acid oxidation of organic acidemias. Plasma amino acid levels were normal ( including glutamine, alanine, citrulline, arginine) and urine for organic acids were normal (Orotic acid, uracil). PCR showed a change in codon 208 of exon 6 from GCA to ACA, as happened in amniotic fluid of his grandsons.
These patients are relatively easy to treat once diagnosed, and no longer are the province of pediatric neurologists alone. PEARL-- female heterozygotes are often asymptomatic or minimally symptomatic.
Differential- of headache progressing tohyperammonemic coma can occur with any disorder of the urea cycle. Hyperammonemic citrin deficiency (citrullinemia type II) usually presents in adulthood, sometimes with sometimes without intrahepatic cholestasis and can result in death. Hyperammonemic coma can occur in hyperornithemia, as well. There are over 300 mutations known. Plasma amino acids can show elevated glutamine, alanine or aspartic acid. Citrulline may be low. Organic acids in the urine can show orotic acid or uracil high. Enzyme assay requires liver biopsy but 80 % of diagnoses are made by sequence analysis at this point.
Thursday, February 07, 2008
Minocycline in ALS
Gordon PH, Moore DH, Miller RG et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.
412 patients were randomized to placebo or minocycline in doses up to 400 mg/day for 9 months. Primary outcome measure was rate of change in the revised ALS functional rating scale (ALSFRS-R). Patients in the minocycline group declined faster and had a trend to declining FVC faster.
Background hypothesis is that minocycline inhibits cell death for apoptosis. It prolongs mice lives in transgenic models of ALS. Trials are done or planned in Parkinson's disease, Huntington's disease, stroke, dementia, and multiple sclerosis. Authors state the "justification for these trials should be reassessed."
Blogger note: Almost simultaneous, ECTRIMS 2007 reported a disappointing trial of minocycline in MS, and Neurology reported a positive trial regarding the use of minocycline in acute ischemic stroke, the details of which are blogged at the link below.
see also blog about minocycline in stroke:
http://strokenotes.blogspot.com/2008/02/minocycline-treatment-for-acute-stroke.html
412 patients were randomized to placebo or minocycline in doses up to 400 mg/day for 9 months. Primary outcome measure was rate of change in the revised ALS functional rating scale (ALSFRS-R). Patients in the minocycline group declined faster and had a trend to declining FVC faster.
Background hypothesis is that minocycline inhibits cell death for apoptosis. It prolongs mice lives in transgenic models of ALS. Trials are done or planned in Parkinson's disease, Huntington's disease, stroke, dementia, and multiple sclerosis. Authors state the "justification for these trials should be reassessed."
Blogger note: Almost simultaneous, ECTRIMS 2007 reported a disappointing trial of minocycline in MS, and Neurology reported a positive trial regarding the use of minocycline in acute ischemic stroke, the details of which are blogged at the link below.
see also blog about minocycline in stroke:
http://strokenotes.blogspot.com/2008/02/minocycline-treatment-for-acute-stroke.html
Monday, February 04, 2008
Succinic semialdehyde dehydrogenase deficiency (SSADH)
Pearl PL, Gibson KM, Acosta MT, et al. Clinical spectrum of SSADH. Neurology 2003; 1413-1417.
Or, how to have at least a little familiarity with this entity. This is based on a review of 51 patients, ages 1-21 at diagnosis.SSADH is also called 4 hydroxy butyric aciduria.
The presentation during childhood is psychomotor seixures, hypotonia, and nonprogressive ataxia, disproportionate language impairment, behavioral abnormalities including aggressiveness, anxiety, hallucinations, and self injurious behavior. Developmental delay, hypotonia, and mental retardation are the major clinical manifestations. Ataxia, behavior problems seizures and hyporeflexia appear in slightly less than half, and the syndrome is slowly or nonprogressive.
EEG shows generalized and focal epileptiform activity, photosensitivity, background slowing,sleep asynchrony, and was normal in about half. MRI showed T2 hyperintensities in the globus pallidus bilaterally and symmetrically.
The treatment is obscure-- the authors discuss the rationale of vigabatrin (nonapproved) in the GHB pathway , notes the Depakote is contraindicated as it inhibits any remaining SSADH. Naloxone reverses GHB-mediated inhibitory effect on striatal dopamine release.
Biochem--SSADH + GABA transaminase convert GABA to succinic acid. In SSADH, GABA instead converts to 4-hydroxybutyrate. GHB accunulates in urine, serum, and CSF of patients. The gene maps to chromosome 6p22. Standard organic acid screens miss the increased excretion of 4-oh- butyric acid. Only a small peak obscured in a large urea peak may appear. It is necessary to add a selective ion monitoring mass spectrometry screen for specific compounds to make the diagnosis.
GHB is an endogenous metabolite and neurotransmitter. It is used to manage cataplexy and opiate and alcohol withdrawl, as a recreational drug of abuse, and to subdue victims for sexual assault. Please see related posts on GHB and toner cartridge abuse.
http://www.blogger.com/post-edit.g?blogID=30837446&postID=1017610194363222736
http://www.blogger.com/post-edit.g?blogID=30837446&postID=1017610194363222736
Or, how to have at least a little familiarity with this entity. This is based on a review of 51 patients, ages 1-21 at diagnosis.SSADH is also called 4 hydroxy butyric aciduria.
The presentation during childhood is psychomotor seixures, hypotonia, and nonprogressive ataxia, disproportionate language impairment, behavioral abnormalities including aggressiveness, anxiety, hallucinations, and self injurious behavior. Developmental delay, hypotonia, and mental retardation are the major clinical manifestations. Ataxia, behavior problems seizures and hyporeflexia appear in slightly less than half, and the syndrome is slowly or nonprogressive.
EEG shows generalized and focal epileptiform activity, photosensitivity, background slowing,sleep asynchrony, and was normal in about half. MRI showed T2 hyperintensities in the globus pallidus bilaterally and symmetrically.
The treatment is obscure-- the authors discuss the rationale of vigabatrin (nonapproved) in the GHB pathway , notes the Depakote is contraindicated as it inhibits any remaining SSADH. Naloxone reverses GHB-mediated inhibitory effect on striatal dopamine release.
Biochem--SSADH + GABA transaminase convert GABA to succinic acid. In SSADH, GABA instead converts to 4-hydroxybutyrate. GHB accunulates in urine, serum, and CSF of patients. The gene maps to chromosome 6p22. Standard organic acid screens miss the increased excretion of 4-oh- butyric acid. Only a small peak obscured in a large urea peak may appear. It is necessary to add a selective ion monitoring mass spectrometry screen for specific compounds to make the diagnosis.
GHB is an endogenous metabolite and neurotransmitter. It is used to manage cataplexy and opiate and alcohol withdrawl, as a recreational drug of abuse, and to subdue victims for sexual assault. Please see related posts on GHB and toner cartridge abuse.
http://www.blogger.com/post-edit.g?blogID=30837446&postID=1017610194363222736
http://www.blogger.com/post-edit.g?blogID=30837446&postID=1017610194363222736
Sunday, February 03, 2008
Rabies transmission through solid organ transplantation
Burton EC, Burns, DK, Opatowsky MJ, El-Fekt WH, et al. Raies encephalomyelitis. Clinical, neuroradiological, and pathologic findings in 4 transplant recipients. Arch Neurol. 2005; 62: 873-882.
Rabies has been transmitted through animal bites, most commonly bats, also through corneal transplants. 4 individuals received organs from a single donor with unsuspected rabies who had suspected cocaine induced agitation. All recipients were readmitted within a month of receiving their organs with symptoms that rapidly progressed to coma and death. Theyincluded sleep deprivation, tremors, decreased appetite, abdominal and back pain, itching (one underwent appendectomy for abdom pain), delirium, myoclonus, and eventually death.
LP done on 3 patients, all had normal glucose, 2 had high protein (69,229), all had increased cells (7-32), all had negative viral cultures.
MRI's were bilaterally abnormal in PVWM, leptomeninges, medial temporal lobes, inferior frontal lobes, subinsular cortex, precentral gyus, basal ganglia, thalami, midbrain, hippocampi , cerebral peduncles and cerebellum. Initial CT's were all normal.
EEG's showed moderate to severe slowing, one patient ultimately had seizures. Diagnosis was made at post mortem.
The cardinal signs of classic rabies encephalitic form are fluctuating consciousness, phobic spasms, and autonomic dysfunction. Bat rabies patients canhave local pain at bite site (burbing, numbness, itching, but might be unknown). Symptoms reported include anisocoria, bilateral ptosis, diplopia, nystagmus, pinpoint pupils, intermittent facial palsy, tremor, and rarely seizures (especially in bat rabies). Also, patients may experience hemiparesis, hemisensory loss, assymmetric reflexes or cranial neuropathies.
Rabies has been transmitted through animal bites, most commonly bats, also through corneal transplants. 4 individuals received organs from a single donor with unsuspected rabies who had suspected cocaine induced agitation. All recipients were readmitted within a month of receiving their organs with symptoms that rapidly progressed to coma and death. Theyincluded sleep deprivation, tremors, decreased appetite, abdominal and back pain, itching (one underwent appendectomy for abdom pain), delirium, myoclonus, and eventually death.
LP done on 3 patients, all had normal glucose, 2 had high protein (69,229), all had increased cells (7-32), all had negative viral cultures.
MRI's were bilaterally abnormal in PVWM, leptomeninges, medial temporal lobes, inferior frontal lobes, subinsular cortex, precentral gyus, basal ganglia, thalami, midbrain, hippocampi , cerebral peduncles and cerebellum. Initial CT's were all normal.
EEG's showed moderate to severe slowing, one patient ultimately had seizures. Diagnosis was made at post mortem.
The cardinal signs of classic rabies encephalitic form are fluctuating consciousness, phobic spasms, and autonomic dysfunction. Bat rabies patients canhave local pain at bite site (burbing, numbness, itching, but might be unknown). Symptoms reported include anisocoria, bilateral ptosis, diplopia, nystagmus, pinpoint pupils, intermittent facial palsy, tremor, and rarely seizures (especially in bat rabies). Also, patients may experience hemiparesis, hemisensory loss, assymmetric reflexes or cranial neuropathies.
Drugs causing myoclonus
Neurololgy 2002; 58:984-985
Antidepressants
MAOI
TCA's
Lithium
Antibiotics
penicillin
ticarcillin
carbenicillin
cephalosporins
Anesthestics
etomidate
enflurane
chloralose
Anticonvulsants
valproic acid
carbamazepine
clozapine
vigabatrin
Calcium channel blockers
verapamil
nifedipine
opiate derivatives
meperidine
methadone
morphine
oxycodone
Other drugs
bismuth
chlorambucil
Overdoses or poisonings
antihistamine overdose
methyl bromide fumes
organic mercury poisoning
gasoline sniffing
dichloroethane ingestion
strychnine poisoning
Antidepressants
MAOI
TCA's
Lithium
Antibiotics
penicillin
ticarcillin
carbenicillin
cephalosporins
Anesthestics
etomidate
enflurane
chloralose
Anticonvulsants
valproic acid
carbamazepine
clozapine
vigabatrin
Calcium channel blockers
verapamil
nifedipine
opiate derivatives
meperidine
methadone
morphine
oxycodone
Other drugs
bismuth
chlorambucil
Overdoses or poisonings
antihistamine overdose
methyl bromide fumes
organic mercury poisoning
gasoline sniffing
dichloroethane ingestion
strychnine poisoning
Friday, February 01, 2008
Paroxysmal extreme pain disorder (formerly familial rectal pain syndrome)
Fertleman CR, Ferrie CD, Aicardi J. Neurology 2007; 69:586-595.
A large family describes episodes in affected individuals of excruciating rectal pain, flushing of the buttocks and legs, ocular pain, flushing of the eyelids, and periorbital skin, and submaxillary pain. Tonic atacks with bradycardia in infancy and apnea and cardiac asystole with these tonic nonepileptic seizures may be part of the syndrome. The onset may even be in utero. Newborns may be stiff and red. The precipitant for the first attack is usually defecation. Other triggers might include bathing, sudden loud noises, feeding and perineal toilet, cold , wind, eating and emotion. Painful attacks can be divided into rectal, ocular and jaw. However, pain is not restricted to these sites. Flushing is a constant feature and accompanies pain in younger individuals. The pain starts as an itch like pain then burning lancinate, stabbing, and becomes unbearable, the worst pain imaginable. Flushes may be geographic but not always. "Harlequin" color changes are common but not universal and may affect half the face. Other symptoms may include hypersalivation with jaw attacks, watering of eyes, weakness of the affected foot for 24 hours, episodic vomiting, and prolonged recovery from inhalational anesthetics. Tonic attacks are associated with harlequin color changes, can last up to a minute, and leads to several minutes of nonresponsiveness. Symptoms between attacks include constipation (due to fear of precipitating an attack).
Treatment with carbamazepine has been shown to be at least partly effective, completely so in a few patients. High doses are used. Opiates are not effective, and amitryptilene and clonidine are not effective. Inhaled nitrous oxide (Entonex) is used for some of the most severe attacks. Tests are always normal, except tachycardia with attacks. EEG during attack shows slow--flat -slow pattern. The channelopathy is a mutant sodium 1.7 channel .
Differentiate from hyperekplexia in which infants are high toned with increased reflexes. Hyperekplexia is associated with a glycine channel disorder. Children do not respond to pacers with aystole suggesting they are of respiratory not cardiac origin. It si not clear if tonic seizures with asystole pose a threat or not (anoxic seizures are benign, hyperecplectic can be fatal). Primary erythromalgia is caused by mutations in sodium channel gene SCN9A with severe pain and flushing, but occur in the feet and are triggered by warm temperature and exercise. It usually occurs in adult life and fails to respond to CBZ whereas mexilitene is helpful. The disease is lifelong but attacks lessen over time in adulthood.
A large family describes episodes in affected individuals of excruciating rectal pain, flushing of the buttocks and legs, ocular pain, flushing of the eyelids, and periorbital skin, and submaxillary pain. Tonic atacks with bradycardia in infancy and apnea and cardiac asystole with these tonic nonepileptic seizures may be part of the syndrome. The onset may even be in utero. Newborns may be stiff and red. The precipitant for the first attack is usually defecation. Other triggers might include bathing, sudden loud noises, feeding and perineal toilet, cold , wind, eating and emotion. Painful attacks can be divided into rectal, ocular and jaw. However, pain is not restricted to these sites. Flushing is a constant feature and accompanies pain in younger individuals. The pain starts as an itch like pain then burning lancinate, stabbing, and becomes unbearable, the worst pain imaginable. Flushes may be geographic but not always. "Harlequin" color changes are common but not universal and may affect half the face. Other symptoms may include hypersalivation with jaw attacks, watering of eyes, weakness of the affected foot for 24 hours, episodic vomiting, and prolonged recovery from inhalational anesthetics. Tonic attacks are associated with harlequin color changes, can last up to a minute, and leads to several minutes of nonresponsiveness. Symptoms between attacks include constipation (due to fear of precipitating an attack).
Treatment with carbamazepine has been shown to be at least partly effective, completely so in a few patients. High doses are used. Opiates are not effective, and amitryptilene and clonidine are not effective. Inhaled nitrous oxide (Entonex) is used for some of the most severe attacks. Tests are always normal, except tachycardia with attacks. EEG during attack shows slow--flat -slow pattern. The channelopathy is a mutant sodium 1.7 channel .
Differentiate from hyperekplexia in which infants are high toned with increased reflexes. Hyperekplexia is associated with a glycine channel disorder. Children do not respond to pacers with aystole suggesting they are of respiratory not cardiac origin. It si not clear if tonic seizures with asystole pose a threat or not (anoxic seizures are benign, hyperecplectic can be fatal). Primary erythromalgia is caused by mutations in sodium channel gene SCN9A with severe pain and flushing, but occur in the feet and are triggered by warm temperature and exercise. It usually occurs in adult life and fails to respond to CBZ whereas mexilitene is helpful. The disease is lifelong but attacks lessen over time in adulthood.
Evaluating dizzy patients-- historical pearls
Presyncope-- brief light headedness when standing with drop in BP
Benign positional vertigo-- lasts second, triggered with head movement especially in AM when getting out of bed or in pm when getting in . However, a few cases lack classical h/s and present with postural dizziness/falls
Vertiginous migraines-- last 10-30 minutes, are insensitive to position, may be followed by a HA
Meniere's related vertigo may last hours, be accompanied by tinnitus and hearing loss, and is not triggered by motion Vestibular neuritis may have a sudden onset and last days . Patients may describe a "floating sensation"
TIA's last a few minutes and are accompanied by other "brainstem" signs
Orthostatic intolerance-- light headed, dizzy, impulse of falling
Basilar occlusion-- rotational vertigo, nonvertiginous dizziness
psychiatric-- panic disorder-- dizzy/woozy, sudden veers
Hypoglycemia-- light headed, unsteady.
Benign positional vertigo-- lasts second, triggered with head movement especially in AM when getting out of bed or in pm when getting in . However, a few cases lack classical h/s and present with postural dizziness/falls
Vertiginous migraines-- last 10-30 minutes, are insensitive to position, may be followed by a HA
Meniere's related vertigo may last hours, be accompanied by tinnitus and hearing loss, and is not triggered by motion Vestibular neuritis may have a sudden onset and last days . Patients may describe a "floating sensation"
TIA's last a few minutes and are accompanied by other "brainstem" signs
Orthostatic intolerance-- light headed, dizzy, impulse of falling
Basilar occlusion-- rotational vertigo, nonvertiginous dizziness
psychiatric-- panic disorder-- dizzy/woozy, sudden veers
Hypoglycemia-- light headed, unsteady.
Thursday, January 31, 2008
Types of headaches
Migraine types-
1. Classic
2. Common
3. Complicated
4. Retinal
5. Opthalmoplegic
6. Benign mydriasis, episodic as a sign of migraine
7. Basilar (Bickerstaff) migraine
8. Hemiplegic
9. Vertiginous
10. Acephalgic
Non migraine headache
11. Tension
12. ebound
13. Cluster
14. Paroxysmal hemicrania (differentiate from cluster partly by female predominance, shorter duration and response to indomethacin)
15. Sunct syndrome-- unresponsive to indomethacin and SUNA syndrome
16.Ice pick headache
17. Ptussive headache (consider relation to Chiari malformation or rarely subdural hematoma)
18. Thunderclap headache
19. Greater occipital neuralgai
20. Hypnic headache
21. Carotid dissection
22. Temporal arteritis
23. Post-traumatic headache
24. Glossopharyngeal neuralgia
25. Intracranial hypertension (with or without pappilledema)
Headaches related to eye disease
26. Corneal erosion/disease
27. Intraocular disease-- include acute angle glaucoma, scleritis, iritis, uveitis.
28. Optic neuritis
29. Eye strain
1. Classic
2. Common
3. Complicated
4. Retinal
5. Opthalmoplegic
6. Benign mydriasis, episodic as a sign of migraine
7. Basilar (Bickerstaff) migraine
8. Hemiplegic
9. Vertiginous
10. Acephalgic
Non migraine headache
11. Tension
12. ebound
13. Cluster
14. Paroxysmal hemicrania (differentiate from cluster partly by female predominance, shorter duration and response to indomethacin)
15. Sunct syndrome-- unresponsive to indomethacin and SUNA syndrome
16.Ice pick headache
17. Ptussive headache (consider relation to Chiari malformation or rarely subdural hematoma)
18. Thunderclap headache
19. Greater occipital neuralgai
20. Hypnic headache
21. Carotid dissection
22. Temporal arteritis
23. Post-traumatic headache
24. Glossopharyngeal neuralgia
25. Intracranial hypertension (with or without pappilledema)
Headaches related to eye disease
26. Corneal erosion/disease
27. Intraocular disease-- include acute angle glaucoma, scleritis, iritis, uveitis.
28. Optic neuritis
29. Eye strain
Tuesday, January 29, 2008
Differential diagnosis of ON
1. Anterior ischemic optic neuropathy (AION) often lacks the pain seen in ON
2. Painless visual loss without improvement over several weeks AION
3. Leber's hereditary optic neuropathy (LHON) occurs inyoung men with a mitochondrial disease; the presentation is unilateral unremitting progressive visual loss to bilateral visual loss over days to months with disc edema, peripappillary telangiectasias, and permanent visual loss.
4. Absent venous pulsations-- enlarged blind spot-- consider increased ICP
5. Orbital mass constricting the optic nerve may cause disc edema, proptosis, and EOM restriction unilaterally
6. Diabetic papillopathy in young diabetics often remits
7. Other inflammatory diseases: HIV, syphilis, TB, cryptococcus, toxoplasma, varicella, histoplasmosis, CMV, and h. zoster all can cause ON.
8. Macular star suggests toxoplasmosis.
9. Optic spinal "Asian" MS may be a form of NMO.
2. Painless visual loss without improvement over several weeks AION
3. Leber's hereditary optic neuropathy (LHON) occurs inyoung men with a mitochondrial disease; the presentation is unilateral unremitting progressive visual loss to bilateral visual loss over days to months with disc edema, peripappillary telangiectasias, and permanent visual loss.
4. Absent venous pulsations-- enlarged blind spot-- consider increased ICP
5. Orbital mass constricting the optic nerve may cause disc edema, proptosis, and EOM restriction unilaterally
6. Diabetic papillopathy in young diabetics often remits
7. Other inflammatory diseases: HIV, syphilis, TB, cryptococcus, toxoplasma, varicella, histoplasmosis, CMV, and h. zoster all can cause ON.
8. Macular star suggests toxoplasmosis.
9. Optic spinal "Asian" MS may be a form of NMO.
Optic neuritis, symptoms and signs
(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
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
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.
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