state and responsive to steroids.
Leger GC,Johnson N,Horowitz SW , et al. Dememtia like presentation of striatal hypermetabolic state with antistriatal antibodies responsive to steroids. Arch Neurol 2004; 61: 757-757.
Case presentation of a 48 year old woman with a one year history of progressive changes in pesonality and attention, originally diagnosed with a frontal dementia. PET showed a hypermetabolic lesion in the left striatum and plasma antistriatal antibodies were found. Treatment with corticosteroids resulted in a return of her premorbid state. PET scan and titers of antibody resolved. the differential diagnosis in this case was Syndenham's chorea and theantiphospholipid antibody state.
the phenotype of Sydenhams is usuallykids with onset of chorea, facial grimacing, hypotonia, and loss of fine control. Elevated ASO titers are present. Mood changes and OCD behavior may occur. Epitypes of IgM ASO titers cros react with striatum. It typically is self-limited and immune modulation may be useful. SLE occassionally occurs.
Sunday, December 02, 2007
Dementia in women preceded by weight loss
Knopman DS et al. Incident dementia in women is preceded by weight loss by at least a decade. Neurology 2007; 69:739-746.
Data is mixed. Weight loss isnoted at diagnosis, but obesity is a risk factor. Weight loss progresses with dementia. The Rochester Epidemiology project. Women began to lose weight 11-20 years prior to onset of dementia.
Data is mixed. Weight loss isnoted at diagnosis, but obesity is a risk factor. Weight loss progresses with dementia. The Rochester Epidemiology project. Women began to lose weight 11-20 years prior to onset of dementia.
Progressive supranuclear palsy.-parkinsonism
Kaat LD, Boon AJW, Kamphorst W etal.,Frontal presentation in PSP. Neurology 2007; 69:723-729
Diagnostic accuracy is poor (70 % initial misdiagnosis, 20 % terminal misdiagnosis). International criteria include falls in first year and vertical supranuclear palsy. PSP parkinsonism is a phenotype with assymmetric onset, tremor, levodopa response and longer disease duration. (see Williams DR et al. Brain 2005). A different phenotype of PSP is behavioral changes with impaired executive functions that may overlap FTD.
Clinical signs that were significant were abnormal score on the Thurstone (word fluency) with results often less than 3 or 5; applause sign in 72 % (http://neurologyminutiae.blogspot.com/search?q=applause+sign), and 85 % were abnormal when detailed cognitive evaluation was performed. These included especially abnormal executive functions, mental slowing, memory disturbance and change in personality.
Unreliable: dyskinesia, cortical sensory loss, dystonia and and cerebellar signs (all < 3 %). The most common misdiagnosis was FTD. Urge incontinence was both significantly higher (2x) than PD and with increased mortality, as was older age. Phenotype did not affect survival. Both had median survival around 8 years. Article suggests importance of Thurstone and personality changes (applause sign) increase the sensitivity of diagnosis.
Diagnostic accuracy is poor (70 % initial misdiagnosis, 20 % terminal misdiagnosis). International criteria include falls in first year and vertical supranuclear palsy. PSP parkinsonism is a phenotype with assymmetric onset, tremor, levodopa response and longer disease duration. (see Williams DR et al. Brain 2005). A different phenotype of PSP is behavioral changes with impaired executive functions that may overlap FTD.
Clinical signs that were significant were abnormal score on the Thurstone (word fluency) with results often less than 3 or 5; applause sign in 72 % (http://neurologyminutiae.blogspot.com/search?q=applause+sign), and 85 % were abnormal when detailed cognitive evaluation was performed. These included especially abnormal executive functions, mental slowing, memory disturbance and change in personality.
Unreliable: dyskinesia, cortical sensory loss, dystonia and and cerebellar signs (all < 3 %). The most common misdiagnosis was FTD. Urge incontinence was both significantly higher (2x) than PD and with increased mortality, as was older age. Phenotype did not affect survival. Both had median survival around 8 years. Article suggests importance of Thurstone and personality changes (applause sign) increase the sensitivity of diagnosis.
Dementia with LB and PDD. Can MRI make difference?
editorial Seppi K, Rascol O. Dementia with lewy bodies and Parkinsondisease with dementia. Can MRI make the difference? Neurology 2007; 69: 717-718 (editorial) and aricle
Beyer MK, Larsen JP, Aarsland D. Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies. Neurology 2007; 69: 747-754.
Article shows DLB had more cortical atrophy than patients with PDD especially in temporal, parietal and occipital lobes. The editorial cites the clinical rule, that if dementia occurs within 12 months of the PD, its DLB, but if more than that, its PDD.
Neuropathology is not always different as both conditions share widespread ubiquitin, alpha synuclein positive neuronal inclusion LB. The editorial cautions that the issue remains unsettled whether DLB and PDD are one or two diseases.
Beyer MK, Larsen JP, Aarsland D. Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies. Neurology 2007; 69: 747-754.
Article shows DLB had more cortical atrophy than patients with PDD especially in temporal, parietal and occipital lobes. The editorial cites the clinical rule, that if dementia occurs within 12 months of the PD, its DLB, but if more than that, its PDD.
Neuropathology is not always different as both conditions share widespread ubiquitin, alpha synuclein positive neuronal inclusion LB. The editorial cautions that the issue remains unsettled whether DLB and PDD are one or two diseases.
Saturday, November 03, 2007
Alz disease and Mediterranean diet
Scarmeas N, Luchsinger JA, Mayeux R, Stern Y. Mediterranean diet and Alzheimer's disease mortality. Neurology 2007; 69:1084-1093.
editorial Galvin JE Pass the grain and spare the brain. Neurology 2007; 69: 1072-1073.
Article states that consuming M diet, consisting of a high intake of cereal, legumes, vegetables, fruits, and fish, with a high unsaturated fatty acid, eg., olive oil is associated with a low intake of saturated fats , dairy products, meat and poultry. moderate wine is consumed with meals.
Adherence to the diet was associated with a lower mortality with a positive dose response effect. Adherence inthe highest tertile led to a 73 % risk reduction and average extra survival or nearly four years. It prevents death from ANY cause. Other studies have shown that exercise and mental stimulation also delay mortality.
editorial Galvin JE Pass the grain and spare the brain. Neurology 2007; 69: 1072-1073.
Article states that consuming M diet, consisting of a high intake of cereal, legumes, vegetables, fruits, and fish, with a high unsaturated fatty acid, eg., olive oil is associated with a low intake of saturated fats , dairy products, meat and poultry. moderate wine is consumed with meals.
Adherence to the diet was associated with a lower mortality with a positive dose response effect. Adherence inthe highest tertile led to a 73 % risk reduction and average extra survival or nearly four years. It prevents death from ANY cause. Other studies have shown that exercise and mental stimulation also delay mortality.
Dementia, estrogens after oopherectomy
Rocca WA et al. Increased risk of cognitive impairment or dementia in women who underwent oopherectomy before menopause. Neurology 2007; 69:1074-1083.
editorialHogervorst E. Should surgical menopausal women be treated with estrogens to decrease the risk of dementia? Neurology 2007; 69: 1070-1071.
article is from Mayo Clinic in Minnesota. Surgical menopause increases the risk of dementia or cognitive impairment by 45 % in a large observation followup trial. With unilateral surgery before age 41, there was double risk, before age 34 there was four times risk, for bilateral surgery before age 46 without treatment there was 82 % increased risk, but if estrogens were given till age 51 (natural menopause age) the risk for dementia was not significant. After age 51, the effects of estrogens were not protective against dementia. A prior study showed a benefit in patients up to age 58 with bilateral surgery. Editorial emphasizes that the effects of treatment are beneficial only for a short period of administration of drug (3-12 months). Estrogens are not indicated for this purpose in women above age 60. The author of the editorial proposed to investigate genetic polymorphisms in women with AD which are associated with altered sex steroid metabolism and synthesis, especially CYP 1B1 (Leu432) and COMT Met/Met to explain why some older women have an increased risk of AD when they receive HRT for a longer period of time.
editorialHogervorst E. Should surgical menopausal women be treated with estrogens to decrease the risk of dementia? Neurology 2007; 69: 1070-1071.
article is from Mayo Clinic in Minnesota. Surgical menopause increases the risk of dementia or cognitive impairment by 45 % in a large observation followup trial. With unilateral surgery before age 41, there was double risk, before age 34 there was four times risk, for bilateral surgery before age 46 without treatment there was 82 % increased risk, but if estrogens were given till age 51 (natural menopause age) the risk for dementia was not significant. After age 51, the effects of estrogens were not protective against dementia. A prior study showed a benefit in patients up to age 58 with bilateral surgery. Editorial emphasizes that the effects of treatment are beneficial only for a short period of administration of drug (3-12 months). Estrogens are not indicated for this purpose in women above age 60. The author of the editorial proposed to investigate genetic polymorphisms in women with AD which are associated with altered sex steroid metabolism and synthesis, especially CYP 1B1 (Leu432) and COMT Met/Met to explain why some older women have an increased risk of AD when they receive HRT for a longer period of time.
Wednesday, May 02, 2007
Criteria for Sporadic CJD
WHO 1998
1. Progressive dementia with any 2 of (myoclonus, pyramidal/EP, visual/cerebrellar/akinetic mutism)
AND
2, typical EEG and/or if 2 year duration + CSF 14,3,3
AND
3. Routine evaluation shows no other diagnosis
UCSF Modified
Rapid Cognitive Decline with any 2 of following: myoclonus, pyramidal/EP, visual, cerebellar, akinetic mutism, other focal cortical signs
AND
typical MRI and/or EEG
Comments of MRI on CJD: 91 % sensitive and 93-95 % specific. Findings include abnormal FLAIR and DWI in cortical gyri (ribboning) especially in CN, PUT and THAL. Only one form of CJD-- the MM2 subtype may not always show the DWI and FLAIR changes. vCJD shows "pulvinar" sign in thalamus.
Reviewing Geschwind's lecture and handout, the most useful table was the "lab finding not consistent with CJD". They include normal DWI and FLAIR, FLAIR without corresponding DWI abnormalities, abnormal contrast enhancement, leukoencephalopathy or significant white matter abnormality not attributable to another condition, mass effect or edema, CSF pleocytosis, CSF protein > 100, or elevated IgG index.
Clinical finding not typically found in CJD included early seizures, significant GI distress, ataxia without cognitive impairment, cranial neuropathy, acute stroke like onset weakness, and chorea. By contrast, aphasia, neglect and other "cortical" findings are common.
Body CT/PET can be considered for cases of possible paraneoplastic syndrome. Sarcoid also can be discovered.
See what's free at AOL.com.
HIV dementia notes (talk A Nath AAN 2007)
1. Post Haart, HIV dementia is seen at higher CD4 counts and the nadir CD4 count is more important than present count.
2. Host genetic factors are important in the development, including genetic mutations in the promoter region of monocyte chemoattractant factor 1 or its receptor CCR2 and TNF alpha.
3. Cognitive slowing and apathy are well known signs. Gait disturbance, bradykinesia, falls, loss of dexterity, and frontal release signs are also well known. Less well known is mania in 5 %, or accompanying myelopathy and symmetric peripheral sensory neuropathy.
4. Distinguishing HIV dementia from effects of drug abuse is important since the latter is unlikely to respond to HAART. Differentiating from effects of HCV is also a challenge especially as HAART drugs are metabolized hepatically.
5. There is increased incidence in older patients and apo E4 alleles and thus an interaction with Alzheimer's disease which can also present in older patients, albeit faster in some cases than it would have otherwise.
6. IRIS patients may have features similar to JC virus and PML but without JC virus detectable in brain or CSF, and IRIS patients may respond partially to steroids.
7. Potent antiretrovirals with 3 or more highly penetrant drugs are the standard of care for most cases of HIV dementia. Highly penetrant drugs include D4T, AZT, ABV, EFV, NVP, IDV.
See what's free at AOL.com.
Sunday, April 22, 2007
Natural history of primary progressive aphasia
Rhun EL et al.Neurology 2005; 65:887-891.
49 patients were diagnosed (France). median age at onset was 62. First visit median age 66. Impaired ADL's occurred within 7 years. 75 % eventually met diagnostic criteria for FTD, 14 % for LBD, 8 % for CBD, 60 % died after median 7 years.
49 patients were diagnosed (France). median age at onset was 62. First visit median age 66. Impaired ADL's occurred within 7 years. 75 % eventually met diagnostic criteria for FTD, 14 % for LBD, 8 % for CBD, 60 % died after median 7 years.
Primary progressive aphasia
Review article Mesulam M-M. Primary progressive aphasia- a language based dementia. NEJM 2003;349-1535-42
Salient points
1. Language only disorder can be present for up to 14 years, or if other deficits are present the language deficit is "salient feature." Complex hobbies such as gardening, sculpting, painting may remain intact. One patient flew his airplane.
2. Differentiate from pure progressive dysarthria or phonologic disintegration (disruption of the formation of words rather than their use); from AD; from FTD with or without AD.
3. "Semantic dementia" refers to patients with a combination of impaired word comprehension and impaired recognition (agnosia) of faces and objects.
4. Clinical picture may vary. "Some patients cannot find the words to express their thoughts. Others cannot understand the meaning of words either seen or heard. Still others cannot name objects. The language can be fluent or nonfluent. (whereas) ...in Alzheimer's disease it is almost always fluent." Some patients may have preserved ability to write language.
5. Anomia is almost always first, later patients may develop agrammatism or develop comprehension problems almost to the point of mutism.
6. Functional imaging has shown greater activation of traditional nonlanguage areas (compensatory areas) during the performance of language tasks.
7. E4 allele is not associated with ppa
8. Chromosome 17 carries the tau gene and is linked to frontotemporal lobar atrophies (Picks or dementia without distinctive histopathology). PPA and frontal lobe dementia may represent anatomically distinct manifestations of a unitary spectrum of degenerative brain diseases. A specific haplotype *H1) of tau gene is overrepresented in patients with the sporadic form of PPA.
9. Pathology of FT degeneration is lobar atrophy, neuronal loss, ubiquitin positive inclusions, tauopathy, occassionally taking the form of Pick bodies.
10. A recent report of 3/4 sibs and 0/12 members of parental generation affected raises the possibility of an aut recessive form of tau-opathy.
11. Voice synthesizers and other technology based devices are useful.
Salient points
1. Language only disorder can be present for up to 14 years, or if other deficits are present the language deficit is "salient feature." Complex hobbies such as gardening, sculpting, painting may remain intact. One patient flew his airplane.
2. Differentiate from pure progressive dysarthria or phonologic disintegration (disruption of the formation of words rather than their use); from AD; from FTD with or without AD.
3. "Semantic dementia" refers to patients with a combination of impaired word comprehension and impaired recognition (agnosia) of faces and objects.
4. Clinical picture may vary. "Some patients cannot find the words to express their thoughts. Others cannot understand the meaning of words either seen or heard. Still others cannot name objects. The language can be fluent or nonfluent. (whereas) ...in Alzheimer's disease it is almost always fluent." Some patients may have preserved ability to write language.
5. Anomia is almost always first, later patients may develop agrammatism or develop comprehension problems almost to the point of mutism.
6. Functional imaging has shown greater activation of traditional nonlanguage areas (compensatory areas) during the performance of language tasks.
7. E4 allele is not associated with ppa
8. Chromosome 17 carries the tau gene and is linked to frontotemporal lobar atrophies (Picks or dementia without distinctive histopathology). PPA and frontal lobe dementia may represent anatomically distinct manifestations of a unitary spectrum of degenerative brain diseases. A specific haplotype *H1) of tau gene is overrepresented in patients with the sporadic form of PPA.
9. Pathology of FT degeneration is lobar atrophy, neuronal loss, ubiquitin positive inclusions, tauopathy, occassionally taking the form of Pick bodies.
10. A recent report of 3/4 sibs and 0/12 members of parental generation affected raises the possibility of an aut recessive form of tau-opathy.
11. Voice synthesizers and other technology based devices are useful.
Thursday, March 29, 2007
Wernicke encephalopathy after bariatric surgery
Singh S and Kumar A. Neurology 68; 807-811 . 2007. Clinical description. review of the literature. 27 cases were found. Most had vomiting as a risk factor, presented with the clinical triad of confusion, ataxia and nystagmus, and had a peripheral neuropathy at a median of two months. Most cases occurred at 4-12 weeks. Other neurologic findings included optic neuropathy, seizures, papilledema, deafness, asterixis, eating avoidance and weakness. Prevalence is around eight percent. Some of the patients had hyperintense signal in the periaqueductal gray and dorsal thalamus. Serum thiamine levels and transketolase levels were variably low. Most patients recovered completely with intravenous thiamine. The pathology has been attributed to thiamine deficit, but that is debated. The amblyopia resembles Leber's and tobacco amblyopia. The deafness may be thalamically based. Vasogenic edema due to free radical production and NMDA mediated neuronal injury may be at fault. In Brazil, the presence of thiaminase in river fish has been attributed. MRI is 53 % SENSITIVE AND 93 % SPECIFIC for the diagnosis. Gastroscopy is prudent to evaluate for stasis.
Saturday, February 03, 2007
Semantic Dementia Lesions
Davies RR, Hodges JR et al. The pathologic basis of semantic dementia. Brain 2005; 128:1984-1995
18 cases with semantic language deficit and associative agnosias and sparing of other aspects oo cognition. 10 men, 8 women, mean onset age 58 mean age of death 68. 8 patients had behavioral disorder including disinhibition, apathy, reduced empathy, stereotypic behavior. Pathologically, 16 had FTD, 13 ubiquitin positive 11 in cortex 2 i inferior olive only; 3 had Picks disease in dentate gyrus, 2 had AD.
Most cased were ubiquitin positive and tau negative. Cases suggest an intriguing overlap with MND
18 cases with semantic language deficit and associative agnosias and sparing of other aspects oo cognition. 10 men, 8 women, mean onset age 58 mean age of death 68. 8 patients had behavioral disorder including disinhibition, apathy, reduced empathy, stereotypic behavior. Pathologically, 16 had FTD, 13 ubiquitin positive 11 in cortex 2 i inferior olive only; 3 had Picks disease in dentate gyrus, 2 had AD.
Most cased were ubiquitin positive and tau negative. Cases suggest an intriguing overlap with MND
Frontotemporal dementia syndromes
Kertesz A et al. The Evolution and Pathology of Frontotemporal dementia Brain 2005 128;1996-2005
Pathology varies. It can include balloon neurons (corticobasal ganglionic degenerations), microtubular tau (50%) and inclusions that are tau negative and ubiquitin positive (50-60 %) also called MND type inclusions. Another group lacks the above and are called dementia lacking distinctive histology. Pick disease has ntracytoplasmic neuronal inclusions, Pick bodies with specific staining in tau in the fascia dentata, hippocampus and cortex.
The clinical phenotypes are FTD-BV (behavioral variant) with loss of behavior and personality; PPA (primary progressive aphasia) with anomia, logopenia and nonfluent speech; corticobasal ganglionic degeneration with unilateral rigidity, apraxia/alien hand and late cognitive change; PSP with vertical gaze palsy, axial rigidity and pseudobulbar palsy with overlap syndromes also.
Of 60 autopsied, 32 had FTD BV, 22 had PPA, 4 had CBGD, 2 had PSP; autopsies however showed MND type inclusions in 18, CBGD in 12, PSP in 3 , Picks in 6, and DLDH in in 6, AD in 10, 5 others showing 1 each of LBD/AD, LBD, Binswanger's d, GSS, and undetermined.
Tau negative pathologies were most likely MND type inclusions, DLDH, and presented with FTD-BV. But PPA, CBGD and semantic dementia appeared.
Tau positive pathology appeared in CBGD, PSP and Picks and presented with PPA CBDS or PSP
Pathology varies. It can include balloon neurons (corticobasal ganglionic degenerations), microtubular tau (50%) and inclusions that are tau negative and ubiquitin positive (50-60 %) also called MND type inclusions. Another group lacks the above and are called dementia lacking distinctive histology. Pick disease has ntracytoplasmic neuronal inclusions, Pick bodies with specific staining in tau in the fascia dentata, hippocampus and cortex.
The clinical phenotypes are FTD-BV (behavioral variant) with loss of behavior and personality; PPA (primary progressive aphasia) with anomia, logopenia and nonfluent speech; corticobasal ganglionic degeneration with unilateral rigidity, apraxia/alien hand and late cognitive change; PSP with vertical gaze palsy, axial rigidity and pseudobulbar palsy with overlap syndromes also.
Of 60 autopsied, 32 had FTD BV, 22 had PPA, 4 had CBGD, 2 had PSP; autopsies however showed MND type inclusions in 18, CBGD in 12, PSP in 3 , Picks in 6, and DLDH in in 6, AD in 10, 5 others showing 1 each of LBD/AD, LBD, Binswanger's d, GSS, and undetermined.
Tau negative pathologies were most likely MND type inclusions, DLDH, and presented with FTD-BV. But PPA, CBGD and semantic dementia appeared.
Tau positive pathology appeared in CBGD, PSP and Picks and presented with PPA CBDS or PSP
Wernicke's encephalopathy
Acute neurologic disorder with the triad of opthalmolegia, ataxia, and confusion, due to thiamine (B1) deficiency. Its probably more common than recognized. Neuroopthalmologic findings are usually horizontal and/or vertical gaze palsy with bilateral abduction deficits, and often, upbeat nystagmus. Mental status changes may be mild. MRI abnormalities may be seen in up to half of patients imaged within two weeks of symptom onset. It may be confirmed by lab testing of erythrocyte ketolase activity. Treatment is 100 mg of thiamine given iv or im with resolution of the symptoms promptly, prevention of Korsakoff's amnesia. MRI deficits may take several days to improve
14,3,3 protein in CJD
Castellani et al. (Case Western Reserve, Italy) studied 90 patients with CJD. IN addition to neurologic deterioration and spongiform deterioration of the brain in sCJD, there is accumulation of proteinase K resistant prion protein (PrP-sc). Most cases are sporadic without prion protein gene (PRNP) or exposure to exogenous prions. The authors classify sCJD based on electropheretic motility of K resistant PrP-sc. Type I sporadic CJD patients are homozygous methionine at codon 129 (sCJDMM1) with phenotype of advanced age, rapid dementia and periodic sharp waves on EEG. sCJDMV1 also has classic phenotype and the two classic forms together account for 70 % of sporadic CJD. The alternate types have a younger age at onset (CJDVV1) ataxia at presentation (sCJDMV2 and sCJDVV2),a slower course and a lack of periodic sharp waves on EEG. The study looked at the sensitivity of 14,3,3 for the different types of sCJD and found an overall sensitivity of 87 %, with 94 % sensitive in classic forms and 57-84 % in nonclassic forms of CJD. Nonclassic presentations are harder to diagnose as they have such symptoms as vertigo, hemianopsia, gait difficulty, and hallucinations. Other tests for CJD include NSE (neuron specific enolase and atu tau protein in CSF). Periodic sharp waves are only present half the time and only the in the midstages of the disease. Nomenclature for the nonclassic forms has included the Heidenham variant (visual symptoms predominate) and Brownell-Oppenheimer variant (cerebellar ataxis is presenting sign). Two other studies in the same issue looked at MRI in sCJD. Shiga et al. looked at 24 cases of 26 that had abnormalities on diffusion weighted imaging (DWI) 3 in striatum,esp caudate, 10 linear lesions in cortex, and 11 in both. 12.5 percent of controls were false positives. In yet another study in same issue, Meissner et al. found that MRI basal ganglia hyperintensity on T2 images are seen in most MV2 cases (variants that may have normal 14,3,3 testing). There was no correlation with basal ganglia abnormality on MRI and eps symptoms. Most patients, whether atypical or not, will have abnormalities on MRI or 14,3,3, testing or both.
14,3,3 protein
Castellani et al. (Case Western Reserve, Italy) studied 90 patients with CJD. IN addition to neurologic deterioration and spongiform deterioration of the brain in sCJD, there is accumulation of proteinase K resistant prion protein (PrP-sc). Most cases are sporadic without prion protein gene (PRNP) or exposure to exogenous prions. The authors classify sCJD based on electropheretic motility of K resistant PrP-sc. Type I sporadic CJD patients are homozygous methionine at codon 129 (sCJDMM1) with phenotype of advanced age, rapid dementia and periodic sharp waves on EEG. sCJDMV1 also has classic phenotype and the two classic forms together account for 70 % of sporadic CJD. The alternate types have a younger age at onset (CJDVV1) ataxia at presentation (sCJDMV2 and sCJDVV2),a slower course and a lack of periodic sharp waves on EEG. The study looked at the sensitivity of 14,3,3 for the different types of sCJD and found an overall sensitivity of 87 %, with 94 % sensitive in classic forms and 57-84 % in nonclassic forms of CJD. Nonclassic presentations are harder to diagnose as they have such symptoms as vertigo, hemianopsia, gait difficulty, and hallucinations. Other tests for CJD include NSE (neuron specific enolase and atu tau protein in CSF). Periodic sharp waves are only present half the time and only the in the midstages of the disease. Nomenclature for the nonclassic forms has included the Heidenham variant (visual symptoms predominate) and Brownell-Oppenheimer variant (cerebellar ataxis is presenting sign). Two other studies in the same issue looked at MRI in sCJD. Shiga et al. looked at 24 cases of 26 that had abnormalities on diffusion weighted imaging (DWI) 3 in striatum,esp caudate, 10 linear lesions in cortex, and 11 in both. 12.5 percent of controls were false positives. In yet another study in same issue, Meissner et al. found that MRI basal ganglia hyperintensity on T2 images are seen in most MV2 cases (variants that may have normal 14,3,3 testing). There was no correlation with basal ganglia abnormality on MRI and eps symptoms. Most patients, whether atypical or not, will have abnormalities on MRI or 14,3,3, testing or both.
Drugs for prion disease
Korth C, Peters PJ Emerging pharmacotherapies for Creutzfeld-Jakob disease. Arch Neurol 2006;63:497-501. Neurological review. Antibodies are protective and heterocyclic small compounds have been proposed as antiprion drugs, leading to clinical trials. Notes from intro-- Variant CJD lasts longer, has younger onset, more psychiatric symptoms, occurs because of the lack of a bovine-human species barrier (which exists with humans and sheep), and concern exists about blood transfusions,organ donations in affected individuals. CJD occurs as sporadic, genetic, and infectious disease. PrP derives from a gene that is expressed by most cell types in the body, but especially CNS and lymphatic organs. After synthesis, PrP(c) (or cellular) is modified postranslationally to receive 2 N linked carbohydrate side chains and a glycosyl phosphatidylinositol membrane anchor, then is sent to the plasma membrane, where it sorts into cholesterol rich detergent resistant membranes (DRM) domains or so called lipid rafts. Membrane anchored PrP can adopt a pathological and infectious conformation PrP(Sc) (scrapie) by a mutation in its amino acid sequence either due to germline or somatic mutation. Once sufficient amount of PrP (sc) is present ("infectious dosage") normal PrP molecules are induced to adopt the PrP(sc) conformation. Cofactors like protein "x" may be essential. Once cascade starts, signal ensue that lead to neuronal death, and pathological hallmarks including plaques and vacuolation. Malluci et al (Science , 2003) showed that knocking out PrP during inoculation of prions, but before replication,could prevent/reverse vacuolization and halt neurological symptoms. Treatment ideas include 1. gene silencing by small RNA interfering targets of PrP expression. 2. Protecting/shielding PrP(c) from conversion by antibodies is proved in animals, but has the problem of constructing an antibody than can cross the blood brain barrier. 3. Destabilizing DRM which is needed for PrP conversion. Possibly statins or quinacrine. 4. Find a competitor to binding on the enzyme "x" which has yet to be identified, which may be necessary to conversion of PrP and misfolding. 5. Inactivating/shielding Prp(sc) so that it is conversion incompetent. Polyanions such as Congo red, dextran, heparin sulfate, and pentosan polysulfate. Pentosan polysulfate is used for cystitis and can be tried, especially if given intrathecally. 6. Conceptually, increase the degradation of the misfolded protein, which has a half life of 28 hours, but unfortunately, the degrading proteins are now unknown. 7. Preventing the neurotoxic effects of PrP(sc), but not known how. Heterocyclic antiprion compounds were identified in cell cultures including phenothiazine and acridine derivatives (quinacrine). Quinacrine was 10x more active than chlorpromazine.
Early signs of GSS syndrome
Arata H. et al. Early clinical signs and imaging findings in Gerstmann-Straussler-Scheinker syndrome (Pro102Leu) There are seven types of inherited prion disease,of which the above is but one accounting for about 28 % of cases. Classic signs of GSS102 are cerebellar signs and slowly progressive dementia, but the ataxia occurs late. Early findings in 11 patients (9 families) are described, including mild gait disturbance, dysesthesias and hyporeflexias of the legs, dysarthria and truncal ataxia and 9/11 had proximal leg weakness. None were demented early. MRI/EEG were normal with abnormal SPECT scans. NCS/EMG were normal. On initial exam only three patients had mild limb ataxia and three others had mild nystagmus. Several were seen/operated for lumbar disease. Two tested had increased 14,3,3, protein in CSF. The problem with orhtopedic referrals was transmission of the disease.
Wednesday, January 31, 2007
Hashimoto's Encephalopathy by other names
Chong Jy and Rowland LP. What's in a NAIM? (editorial) Arch Neurol 2006 63:175-176
Hashimoto's encephalopathy (named by Lord Brain) is also called by "steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT)" or "nonvasculitic autoimmune meningoencephalitis (NAIM). CJD may present identically except without steroid responsiveness.
Hashimoto's encephalopathy (named by Lord Brain) is also called by "steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT)" or "nonvasculitic autoimmune meningoencephalitis (NAIM). CJD may present identically except without steroid responsiveness.
Monday, January 29, 2007
TGA Mechanism
Bartsch T et al. Brain 2006;129:2874-2884. Selective affection of hippocampal CCA-1 neurons in patients with TGA without long term sequelae.
71 percent occurred after physical exertion, stress, Vasalva, or postural changes, most in the morning or afternoon. Of 41 patients, 29 had 36 DWI lesions and corresponding T2 lesions in hippocampus 48-72 hours after , almost all (34/36) in CA1 secotr, one in CA3 sector and one in cornu ammonis. Left sided lesions favored 20-16 with episodic verbal deficits seen in those tested acutely and visuospatial deficits in those with right sided lesions tested acutely. MRI lesions did not persist.
A hypoplastic transverse sinus with slight left sided predominance was seen in 88 %
71 percent occurred after physical exertion, stress, Vasalva, or postural changes, most in the morning or afternoon. Of 41 patients, 29 had 36 DWI lesions and corresponding T2 lesions in hippocampus 48-72 hours after , almost all (34/36) in CA1 secotr, one in CA3 sector and one in cornu ammonis. Left sided lesions favored 20-16 with episodic verbal deficits seen in those tested acutely and visuospatial deficits in those with right sided lesions tested acutely. MRI lesions did not persist.
A hypoplastic transverse sinus with slight left sided predominance was seen in 88 %
Neurologic cosequences of starvation
Basoglu M et al. Neurological consequences of prolonged hunger strike. Eur J Neurol 2006; 13; 1089-1097.
Extensive studies were carried out of Turkish hunger strikers. Patients typically developed gaze evoked nystagmus (vertical in 9/41), limb ataxia in 3, and lateral rectus palsy in 14. All had muscle atrophy but only 11 were demonstrably weak. 15 had paresthesias, and 17 had abnormal vibratory or position sense. All patients were treated with thiamine when they reached the point of confusion. Nystagmus and ataxia resolved, sensory function normalized, but anterograde and retrograde amnesia remained in all.
Michael Rubin commented that although Wernicke-Korsakoff s. was diagnosed in all, osmotic myelinolysis with shift from normonatremic to hypernatremic state was reported in an Algerian hunger striker (Neurology 2005; 64;574-5).
Extensive studies were carried out of Turkish hunger strikers. Patients typically developed gaze evoked nystagmus (vertical in 9/41), limb ataxia in 3, and lateral rectus palsy in 14. All had muscle atrophy but only 11 were demonstrably weak. 15 had paresthesias, and 17 had abnormal vibratory or position sense. All patients were treated with thiamine when they reached the point of confusion. Nystagmus and ataxia resolved, sensory function normalized, but anterograde and retrograde amnesia remained in all.
Michael Rubin commented that although Wernicke-Korsakoff s. was diagnosed in all, osmotic myelinolysis with shift from normonatremic to hypernatremic state was reported in an Algerian hunger striker (Neurology 2005; 64;574-5).
CATIE-AD study
Schneider LS etr al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. NEJM 2006; 355:1533-1538.
Design 421 patients with average MMSE 15 enrolled at 42 sites. Subjects were randomized to placebo, 5.5 mg/d olanzepine, 1 mg/day risperidone, or 56.5 mg/day of quetiapine. Endpoint was the time until the physician switched the medication. Results were not significantly different in the various groups except on minor measures. AE's included higher eps in patients receiving risperidone or olanzepine, and sedation with olanzepine and quetiapine (more than risperidone). Cognitive disturbances were higher in patients on olanzepine (7%) and increased agitation in those getting quetiapine.
In Neurology Alert, Norman Relkin comments that treatment of psychosis in AL is not a matter of writing a drug, but looking at all drugs, precipitants, sleep wake cycle and nutrition, supportive environment and caregiver education, none of which were controlled for. The study did not show the antipsychotic drugs were ineffective, just that they have risks as well. The lay press has misinterpreted the results.
Design 421 patients with average MMSE 15 enrolled at 42 sites. Subjects were randomized to placebo, 5.5 mg/d olanzepine, 1 mg/day risperidone, or 56.5 mg/day of quetiapine. Endpoint was the time until the physician switched the medication. Results were not significantly different in the various groups except on minor measures. AE's included higher eps in patients receiving risperidone or olanzepine, and sedation with olanzepine and quetiapine (more than risperidone). Cognitive disturbances were higher in patients on olanzepine (7%) and increased agitation in those getting quetiapine.
In Neurology Alert, Norman Relkin comments that treatment of psychosis in AL is not a matter of writing a drug, but looking at all drugs, precipitants, sleep wake cycle and nutrition, supportive environment and caregiver education, none of which were controlled for. The study did not show the antipsychotic drugs were ineffective, just that they have risks as well. The lay press has misinterpreted the results.
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