Opherk C, Hirsch LJ. Neurology 2002; 58: 636-8.
Quick and dirty: Documenting an increase in HR during a spell of unresponsiveness usually can differentiate epileptic and psychogenic seizures. Study included 67 epileptic seizure patients and 38 psychogenic seizure patients. Analysis was of quiet staring spells. The positive predictive value was 97 % by using a cutoff of 30 % over baseline.
AAN 2010: PO5:212 Periictal heart rate changes in patients with localization related epilepsy. Jeong et al. 33 patients. HR changes were observed in 70 % of seizures, usually tachycardia. (66% TACHYCARDIA, 4 % BRADYCARDIA) more often in right sided epilepsy than left (77v. 50 %) more in nonlesional than lesional epilepsy (82 v. 45 %) and much earlier in mesial TLE than extratemporal epilepsy ( -54 v. -6 seconds) which may be useful to predict an epileptic event.
Tuesday, February 12, 2008
Monday, February 11, 2008
Singing paraplegia: a distinctive manifestation of spinal dural arteriovenous fistula
Khurana VG, Perez-Terzic CM, Peterson RC et al. Neurology 2002; 58: 1279-1281
Case is included because of the extreme difficulty diagnosing spinal dural av fistulas. They may be worse with upright posture, ambulation, pregnancy and menstruation.
The case is a baritone who had a progressive myelopathy with recurrent paraplegia while singing. (He changed from singing while standing to singing while sitting). He had had insidious bilateral leg weakness while bending forward, without pain or bowel or bladder dysfunction. He did have chronic numbness and paresthesias in his feet. He had T2 signal change in mid to low thoracic area, later from T7 to conus with an enlarged cord. A spinal angiogram showed the fistula with an arterialized vein. The fistula was obliterated surgically and the patient became much better, ambulated better and could sing while standing.
The authors discuss that the slowly progressive myelopathy is due to chronic venous hypertension with postnidal venous engorgement and intraparenchymal cord edema and ischemia. Despite the location of the fistula itself, the MRI changes are almost always in the lower cord , attributed to orthostasis and exacerbated with ambulation. In this case, increased venous presure with Vasalva (respiratory exertion during singing) exacerbated venous engorgement and cord edema and ischemia (the pathogenesis involves "marginal" venous drainage).
Common misdiagnoses include disc herniation, canal stenosis, Guilian Barre syndrome, subacute combined degeneration, transverse myelitis, or spinal cord neoplasia. Many misdiagnoses lead to irreversible neurologic changes.
Case is included because of the extreme difficulty diagnosing spinal dural av fistulas. They may be worse with upright posture, ambulation, pregnancy and menstruation.
The case is a baritone who had a progressive myelopathy with recurrent paraplegia while singing. (He changed from singing while standing to singing while sitting). He had had insidious bilateral leg weakness while bending forward, without pain or bowel or bladder dysfunction. He did have chronic numbness and paresthesias in his feet. He had T2 signal change in mid to low thoracic area, later from T7 to conus with an enlarged cord. A spinal angiogram showed the fistula with an arterialized vein. The fistula was obliterated surgically and the patient became much better, ambulated better and could sing while standing.
The authors discuss that the slowly progressive myelopathy is due to chronic venous hypertension with postnidal venous engorgement and intraparenchymal cord edema and ischemia. Despite the location of the fistula itself, the MRI changes are almost always in the lower cord , attributed to orthostasis and exacerbated with ambulation. In this case, increased venous presure with Vasalva (respiratory exertion during singing) exacerbated venous engorgement and cord edema and ischemia (the pathogenesis involves "marginal" venous drainage).
Common misdiagnoses include disc herniation, canal stenosis, Guilian Barre syndrome, subacute combined degeneration, transverse myelitis, or spinal cord neoplasia. Many misdiagnoses lead to irreversible neurologic changes.
Results of radiotherapy for drooling in ALS
Stalpers LJA, Moser EC. Neurology 2002; 58: 1308.
19 patients with ALS and sialorrhea were treated, all had failed anticholinergic drugs. They got 12 Gy in 2 fractions once a week. That is equivalent to 16 Gy in 8 fractions. 74 % had a complete or partial response. AE's included parotid area pain and mouth dryness. (Netherlands).
Blogger comment question: Can one dare use botox in ALS patients?
19 patients with ALS and sialorrhea were treated, all had failed anticholinergic drugs. They got 12 Gy in 2 fractions once a week. That is equivalent to 16 Gy in 8 fractions. 74 % had a complete or partial response. AE's included parotid area pain and mouth dryness. (Netherlands).
Blogger comment question: Can one dare use botox in ALS patients?
Late onset Friedreich ataxia: phenotypic analysis, MRI findings and review of the literature
Bhidayasiri R, Perlman SL, Pulst SM, Geschwind DH. Arch Neurol 2005; 62: 1865-1869.
Definition: age greater than 25, associated with expansion of GAA repeats in the 1st intron of the X25 gene on chromosome 9.
13 patients are described. All had gait and limb ataxia. Many had dysarthria, oss of vibratory sense and abnormal eye movements. More often they had lower limb spasticity, retained reflexes and no sphincter disturbance or cardiomyopathy. Many had vermian cerebellar atrophy. The authors conclude that patients with the above presentation should be tested for GAA expansion in the FA gene.
This contrasts to the Quebec Cooperative Study criteria that defined FA as beginning before age 20 or the Harding criteria that defined FA as having onset before age 25. LOFA overall had more retained reflexes, slower progression, present neuropathy on nerve conduction testing, and less associated conditions (diabetes, scoliosis and cardiomyopathy).
Definition: age greater than 25, associated with expansion of GAA repeats in the 1st intron of the X25 gene on chromosome 9.
13 patients are described. All had gait and limb ataxia. Many had dysarthria, oss of vibratory sense and abnormal eye movements. More often they had lower limb spasticity, retained reflexes and no sphincter disturbance or cardiomyopathy. Many had vermian cerebellar atrophy. The authors conclude that patients with the above presentation should be tested for GAA expansion in the FA gene.
This contrasts to the Quebec Cooperative Study criteria that defined FA as beginning before age 20 or the Harding criteria that defined FA as having onset before age 25. LOFA overall had more retained reflexes, slower progression, present neuropathy on nerve conduction testing, and less associated conditions (diabetes, scoliosis and cardiomyopathy).
Saturday, February 09, 2008
Blast injuries (including neurologic complications)
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
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
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.
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