NEUROLOGY 2009;72:1056-1061
17 patients (10%) with low levels of Aβ1-42 and very high levels of tau and p-tau. More with moderate levels of tau were found, plus controls.
High tau and p-tau levels negatively correlated with category fluency and VAT test, not with other neuropsych tests (TMT A and B, digit span forward and backward).
Monday, November 30, 2009
Sunday, November 29, 2009
bv variant of FTD
NEUROLOGY 2009;72:732-737 Sensitivity of current criteria
Consensus Criteria published in 1998 by Neary and colleagues.4
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554.[Abstract/Free Full Text]
However, not all patients have all five core features: loss of insight, emotional blunting, impaired personal conduct, decline in social interpersonal conduct, and insidious onset. Loss of insight and emotional blunting were the ones least likely to be represented
Secondary criteria such as speech problems upt o mutism occurred in less than half.
Consensus Criteria published in 1998 by Neary and colleagues.4
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546–1554.[Abstract/Free Full Text]
However, not all patients have all five core features: loss of insight, emotional blunting, impaired personal conduct, decline in social interpersonal conduct, and insidious onset. Loss of insight and emotional blunting were the ones least likely to be represented
Secondary criteria such as speech problems upt o mutism occurred in less than half.
Saturday, November 28, 2009
CSF biomarkers and Alzheimer's disease
A. E. van der Vlies, MSc, N. A. Verwey, MD , F. H. Bouwman, MD, PhD , M. A. Blankenstein, PhD , M. Klein, PhD , P. Scheltens, MD, PhD and W. M. van der Flier, PhD
From : To investigate the relationship between CSF biomarkers and cognitive profiles in Alzheimer disease (AD).
Methods: We included 177 patients with AD. Digit Span, Visual Association Test (VAT), VAT object naming, Trail Making Test (TMT), and category fluency were used to assess cognitive functions. Disease severity was assessed using Mini-Mental State Examination; functional impairment was rated by Clinical Dementia Rating. In CSF, levels of amyloid-beta 1-42 (Aβ1-42), tau, and tau phosphorylated at threonine 181 (p-tau) were measured. K-means cluster analysis was performed with the three biomarkers to obtain three clusters. Multivariate analysis of variance for repeated measures was performed with CSF cluster as between-subjects factor, neuropsychological z scores as within-subjects variable, and age, sex, and education as covariates.
Results: Cluster 1 consisted of 88 patients (49%) with relatively high levels of Aβ1-42 and low levels of tau and p-tau. Cluster 2 contained 72 patients (41%) with relatively low levels of Aβ1-42 and high levels of tau and p-tau. Cluster 3 was made up of 17 patients (10%) with low levels of Aβ1-42 and very high levels of tau and p-tau. No differences between clusters on age, sex, education, APOE genotype, disease duration, functional impairment, or disease severity were found. Patients in cluster 3 performed worse on VAT, TMT-A and -B, and fluency.
Conclusions: Clusters of CSF biomarker levels are related to cognitive profiles in Alzheimer disease. A subgroup of patients with extremely high CSF levels of tau and tau phosphorylated at threonine 181 shows a distinct cognitive profile with more severe impairment of memory, mental speed, and executive functions, which cannot be explained by disease severity.
Politics of health care reform distort reality
The October 29, 2009 issue of the New England Journal of Medicine contains four separate articles on health care issues which, if taken in their entirety, represent the absurdity to which the health care debates in the United States have gone.
The first article-- the best of the four-- describes how much FDA information never reaches clinicians (1). Clinicians and the public rely on the Food and Drug Administration (FDA) for drug and product approvals and denials, and for disseminating accurate information about drugs in their product inserts. I learned that the lengthy, often poorly written and weakly summarized debates about drugs are posted publicly at www.accessdata.fda.gov/scripts/cder/drugsatfda/. The authors cited glaring examples of critical information that somehow was not included in the product labels. Zometa (zoledronic acid, Novartis), used to treat hypercalcemia of malignancy, at the 8 mg dose, caused more renal toxicity and death than the 4 mg dose and was no more effective. Nonetheless, the labelling suggested using the higher dosage "in refractory cases." The product label did not mention increased mortality at the higher dose.
Lunesta (eszopiclone, Sepracor), sold 800 million dollars last year with the help of a direct to consumers marketing campaign. Yet the efficacy data, buried on page 306 of 403, shows patients slept 15 minutes earlier and 37 minutes longer than placebo, with no clinically meaningful improvement in next day alertness or functioning. Similarly, Rozerem (ramelteon), another approved sleep drug, caused younger adults to fall asleep 14 minutes earlier, and older ones 7 minutes earlier, with no improvement on subjective assessments of sleep quality.
The very next article details ways the same government can "further" improve health care. Victor Fuchs (2). advocates incremental rather than radical health care reform. The first of his four proposed reforms is to eliminate employer based health care coverage tax exemptions. The purpose is to raise 200 billion dollars in new revenues, that is taxes, to make the tax system "fairer" since the tax benefit is a regressive tax. He alleges it benefits the wealthy. (Wait a minute-- my practice employs 15 people, who have relatively low incomes and have the same insurance I have. A biller who had breast cancer last year would never have gotten treatment without our comprehensive health insurance). This would allow the creation of insurance exchanges, the second idea, that would, using Fuchs' words, be not as "generous" to "consumers" (actually, sick patients) as the private plans they replace. Supposedly, these exchanges would decrease "broker" costs.
The third, chilling suggestion of Fuchs is the appointment of an "expert" commission to devise changes to the ways Medicare reimburses providers. Fuchs cites "special interests" as blocking the "public good," as a charged way to rally the troops. Again, citing my own practice, with 50 % overhead, a 10 % payment cut equals a 20 % loss of income. Could it be, that by going after providers who have already been sucked dry, Fuchs will drive people out of practice, resulting in fewer providers, thereby raising the cost of care? Fuchs' final idea is an office for technology assessment that would be "quasi-independent." Of whom, I might ask.
The third article-- the last to be reviewed here- describes implementing evidence based medicine in Washington state (3). The state has total authority, except where prohibited by federal statute, to use evidence based methods to assess drugs, devices, surgical procedures, diagnostic tests, imaging procedures, and medical equipment. The author decries the political "pressure" wrought by patients who testify that the benefitted from a technology the state wants to eliminate. Obscenely, the same authors equate pharmaceutical direct to patient marketing with physician "autonomy" and "financial incentive" in ordering tests.
The authors note the "challenges" of this policy, citing the example that thymectomy of myasthenia gravis, used since 1912, has never undergone a rigorous trial. This author will note a few more nonevidence based treatments: penicillin for infection, appendectomy for appendicitis, and burr holes for subdural hematomas of the brain. Are these procedures necessary? Shall the government be in a position to decide? May I be so impudent to suggest satisfaction surveys be returned for all cases of physician assisted suicide?
The assumption of evidence based medicine is that care from one can be generalized to another and is equivalent to another. Evidence is important, and can help us learn how to be better doctors. But, evidence is not the be all and end all. Sometimes doctors have to take the controls from the nurse practitioners and PhD's and make decisions that are in the best interests of the patient. The reasons may not be obvious to the lay public but may be based on sound understanding of pathophysiology. Experience and judgment, absent from these vacuous bureaucratic declarations, still are what most patients seek.
1. Schwartz LM, Woloshin S. Lost in transmission: FDA drug information that never reaches clinicians. N Engl J Med 2009; 361:1717-1720.
2. Fuchs VR. Four health care reforms for 2009. N Engl. J Med 2009; 361: 1720-1722.
3. Franklin GM, Budenholzer BR. Implementing evidence based health policy in Washington State. N Engl J Med 2009; 361:1722-1725.
The first article-- the best of the four-- describes how much FDA information never reaches clinicians (1). Clinicians and the public rely on the Food and Drug Administration (FDA) for drug and product approvals and denials, and for disseminating accurate information about drugs in their product inserts. I learned that the lengthy, often poorly written and weakly summarized debates about drugs are posted publicly at www.accessdata.fda.gov/scripts/cder/drugsatfda/. The authors cited glaring examples of critical information that somehow was not included in the product labels. Zometa (zoledronic acid, Novartis), used to treat hypercalcemia of malignancy, at the 8 mg dose, caused more renal toxicity and death than the 4 mg dose and was no more effective. Nonetheless, the labelling suggested using the higher dosage "in refractory cases." The product label did not mention increased mortality at the higher dose.
Lunesta (eszopiclone, Sepracor), sold 800 million dollars last year with the help of a direct to consumers marketing campaign. Yet the efficacy data, buried on page 306 of 403, shows patients slept 15 minutes earlier and 37 minutes longer than placebo, with no clinically meaningful improvement in next day alertness or functioning. Similarly, Rozerem (ramelteon), another approved sleep drug, caused younger adults to fall asleep 14 minutes earlier, and older ones 7 minutes earlier, with no improvement on subjective assessments of sleep quality.
The very next article details ways the same government can "further" improve health care. Victor Fuchs (2). advocates incremental rather than radical health care reform. The first of his four proposed reforms is to eliminate employer based health care coverage tax exemptions. The purpose is to raise 200 billion dollars in new revenues, that is taxes, to make the tax system "fairer" since the tax benefit is a regressive tax. He alleges it benefits the wealthy. (Wait a minute-- my practice employs 15 people, who have relatively low incomes and have the same insurance I have. A biller who had breast cancer last year would never have gotten treatment without our comprehensive health insurance). This would allow the creation of insurance exchanges, the second idea, that would, using Fuchs' words, be not as "generous" to "consumers" (actually, sick patients) as the private plans they replace. Supposedly, these exchanges would decrease "broker" costs.
The third, chilling suggestion of Fuchs is the appointment of an "expert" commission to devise changes to the ways Medicare reimburses providers. Fuchs cites "special interests" as blocking the "public good," as a charged way to rally the troops. Again, citing my own practice, with 50 % overhead, a 10 % payment cut equals a 20 % loss of income. Could it be, that by going after providers who have already been sucked dry, Fuchs will drive people out of practice, resulting in fewer providers, thereby raising the cost of care? Fuchs' final idea is an office for technology assessment that would be "quasi-independent." Of whom, I might ask.
The third article-- the last to be reviewed here- describes implementing evidence based medicine in Washington state (3). The state has total authority, except where prohibited by federal statute, to use evidence based methods to assess drugs, devices, surgical procedures, diagnostic tests, imaging procedures, and medical equipment. The author decries the political "pressure" wrought by patients who testify that the benefitted from a technology the state wants to eliminate. Obscenely, the same authors equate pharmaceutical direct to patient marketing with physician "autonomy" and "financial incentive" in ordering tests.
The authors note the "challenges" of this policy, citing the example that thymectomy of myasthenia gravis, used since 1912, has never undergone a rigorous trial. This author will note a few more nonevidence based treatments: penicillin for infection, appendectomy for appendicitis, and burr holes for subdural hematomas of the brain. Are these procedures necessary? Shall the government be in a position to decide? May I be so impudent to suggest satisfaction surveys be returned for all cases of physician assisted suicide?
The assumption of evidence based medicine is that care from one can be generalized to another and is equivalent to another. Evidence is important, and can help us learn how to be better doctors. But, evidence is not the be all and end all. Sometimes doctors have to take the controls from the nurse practitioners and PhD's and make decisions that are in the best interests of the patient. The reasons may not be obvious to the lay public but may be based on sound understanding of pathophysiology. Experience and judgment, absent from these vacuous bureaucratic declarations, still are what most patients seek.
1. Schwartz LM, Woloshin S. Lost in transmission: FDA drug information that never reaches clinicians. N Engl J Med 2009; 361:1717-1720.
2. Fuchs VR. Four health care reforms for 2009. N Engl. J Med 2009; 361: 1720-1722.
3. Franklin GM, Budenholzer BR. Implementing evidence based health policy in Washington State. N Engl J Med 2009; 361:1722-1725.
Friday, November 27, 2009
HIV dementia scales
HIV dementia scale
HIV modified dementia scale
Mental alternation test
Sloane Kettering Scale for AIDS dementia complex
Apathy evaluation scale
neuropsychological predictors of poor driving in Alzheimer's disease
Benton Visual Retention Test
Complex Figure Test Copy
Trails A
Functional Reach Test
from Neurology 2009 Feb Dawson et al. (Iowa)
Monday, November 09, 2009
lbd PEARLS
1. RBD is common and fairly specific for synucleinopathy, LBD or MSA
2. Cognitive testing not that bad, memory not that bad, visuospatial especially copying is very bad
3. Parkinson's is atypical
4. Fluctuations with Mayo Fluctuations Scale
5. Profound sleepiness during day
6. Utility of Pet scans "debated"
2. Cognitive testing not that bad, memory not that bad, visuospatial especially copying is very bad
3. Parkinson's is atypical
4. Fluctuations with Mayo Fluctuations Scale
5. Profound sleepiness during day
6. Utility of Pet scans "debated"
Semantic dementia pearls
1. Naming problems, esp anomic
2. left anterior temporal atrophy esp inferolateral
3. good delayed recall
4. homologous contralateral involvement occurs
5. positive family history dementia and ALS is common
6. Behavioral changes ubiquitous later on
7. FTLD pathology
PNFA pearls
1. slowly progressive, lifespan of 20 + years
2. check oromotor apraxia "Lick your lips" "pa-ta-ka, pa-ta-ka"
3. Otherwise normal neuropsych
4. +/- Pet may show left insular/perisylvian abnormality
5. young age 40-80
6. tauopathy like PSP or CBD
7. up-down reversals
8. normal MRI
2. check oromotor apraxia "Lick your lips" "pa-ta-ka, pa-ta-ka"
3. Otherwise normal neuropsych
4. +/- Pet may show left insular/perisylvian abnormality
5. young age 40-80
6. tauopathy like PSP or CBD
7. up-down reversals
8. normal MRI
Saturday, October 17, 2009
depression scales other scales for PD, AD and MS
http://www.mhsfopcls.com/downloads/ger_dep_scl.pdf Geriatric Depression scale
http://www.ibogaine.desk.nl/graphics/3639b1c_23.pdf Beck Depression inventory- pref in Parkinson's disease
Other scales
http://www.nysaaaa.org/Caregiver_Forum/CaregiverForumErieHandout09.pdf caregiver burden assessment
MFIS with link to MSQLI (Connie is this different than MSQOL and how?)
link to links to many clinical tools in MS research
http://www.mdvu.org/library/ratingscales/pd/updrs.pdf updrs and scwab (parkinson;s)
http://www.alegent.com/documents/Sleep_eval.pdf berlin and epworth sleep questionnaire
http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/clock_drawing_test.pdf clock drawing and mini cog (= 3 word recall)
http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/instrumental_activities.pdf Instrumental activities of daily livving (IADL)
http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/phys_selfmain.pdf physical self maintenance scale
http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/function_status_questionnai.pdf (last page is functional activities questionnaire)
http://www.mocatest.org/ Moca-- has links for multiple languages
http://www.neurotransmitter.net/alzheimerscales.html link to MANY Alz assessment tools, behavior and otherwise a few linked below
http://strokecenter.org/trials/scales/blessed_dementia.html blessed dementia scale
http://www.aafp.org/afp/2002/0601/p2263.html CBI, IADL, NPI
Saturday, June 06, 2009
CAA with inflammation clinical characteristics
Kinnecom C et al. Course of cerebral amyloid angiopathy related inflammation. Neurology 2007; 68: 1411-1416.
CAA, amyloid angiopathy, dementia, seizures, HA, T2 hyperintensities, MRI lesions with edema, neuropath with consistent with inflammation, response to decadron, monophasic, or relapsing course.
Lesions were primarily white matter and could be unilateral. 7/12 had monophasic improvement with treatment, 3/12 relapsed, 2/12 were not responsive. Apo E4/E4 was present in 10/12 of CAA with inflammation v. 5.1 % of symptomatic CAA without inflammation.
The suspicion is that this represents inflammation against amyloid deposits and that it strikingly resembles the encephalitis seen in those given Alzheimer's amyloid vaccines.
CAA, amyloid angiopathy, dementia, seizures, HA, T2 hyperintensities, MRI lesions with edema, neuropath with consistent with inflammation, response to decadron, monophasic, or relapsing course.
Lesions were primarily white matter and could be unilateral. 7/12 had monophasic improvement with treatment, 3/12 relapsed, 2/12 were not responsive. Apo E4/E4 was present in 10/12 of CAA with inflammation v. 5.1 % of symptomatic CAA without inflammation.
The suspicion is that this represents inflammation against amyloid deposits and that it strikingly resembles the encephalitis seen in those given Alzheimer's amyloid vaccines.
Monday, March 16, 2009
Thursday, February 26, 2009
Predictors of bad driving in AD
Dawson et al. Neurology 2009; 72: 521-527.
Lane violations were the commonest driving error/safety violation in patients.
Neuropsych measures that correlated best with safety errors were: Benton Visual Retention Test, Complex Figure Test copy, Trails A and Functional Reach Test.
Sunday, June 01, 2008
VGKC autoantibodies mimicking CJD
Tan KM, Lennon VA, Klein CJ, Boeve BF, Pittock SJ. Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology 2008; 70: 1883-1890.
VGKC antibodies have been described in a variety of patient types, and may present with a symptom c0mplex including cognitive impairment and myoclonus, mimicking Creutzfeld-Jacob disease, which is untreatable. Some cases of VGKC may be treatable with IVIG or other anti-immune strategies.
Paraneoplastic VGKC have been identified as paraneoplastic antibodies in neuroendocrine tumors (including small cell lung cancer), retinoblastoma, oligodendroglioma, melanoma, leiomyosarcoma, and hematologic malignancies. They are also seen as markers of neuromyotonia, Morvan's, epilepsy, limbic encephalits, and dysautonomia with hyperhidrosis and GI dysmotility. Animal passive transfer experiments suggest pathogenicitiy. IVIG and plasma exchange are beneficial.
Among 80 patients in this Mayo Clinic series, was usually an inflammatory or neurodegenerative disease. 11 were correctly thought to have autoimmune encephalopathy, 10 with CJD, 5 with viral encephalitis, 3 with recurrent TGA, 4 with psychiatric (anxiety disorder/panic attacks/ conversion disorder). Examination showed frontosubcortical involvement, pesonality change, executive dysfunction, disinhibition, visual hallucinations (10%), agitation or depression. Short term memory impairment, with 58 % having some form of seizure disorder (all types seen) . Cranial nerve involvement was seen in 19 % including diplopia (not MG associated), dysarthria, dysphagia, vision loss, hemifacial spasm, hyperphagia, hyponatremia, EPS, cerebellar ataxia, recurrent ON without NMO antibodies, myoclonus, hypersomnia, autonomic dysfunction. MRI's showed abnormalities in bilateral hippocampi, CN head, splenium , frontal lobe, or multifocal suspicious for CJD. MRI improved partly or wholly. SPECT, EEG, CSF generally or often abnormal. 47% had documented neoplasia, of whom 76 % were smokers, and VGKC preceded diagnosis by five or more months.
Coexisting antibodies included ANNA-1, PCA2, amphiphysin IgG, CRMP 5 IgG with ultimate diagnosis of 5 small cell lung CA, three thymic CA, four prostate adenoCA, Becelllymphoma, CLL, mycosis fungoides, 3 head and neck CA, one colonic adenoca. There also were benign neoplasia including 5 pituitary adenoca, one adrenal, one colonic, one parathyroid, one renal oncocytoma, one gastric leiomyoma. Other AI disorders were Hashimoto titers in 15, endocrine pancreas in 8, and pernicious anemia. 89 % improved with treatment, half dramatically so, including 8 of 10 with initial misdiagnosis of CJD. These included six patients with increased 14,3,3 or NSE, 5 of whom improved remarkably.
VGKC antibodies have been described in a variety of patient types, and may present with a symptom c0mplex including cognitive impairment and myoclonus, mimicking Creutzfeld-Jacob disease, which is untreatable. Some cases of VGKC may be treatable with IVIG or other anti-immune strategies.
Paraneoplastic VGKC have been identified as paraneoplastic antibodies in neuroendocrine tumors (including small cell lung cancer), retinoblastoma, oligodendroglioma, melanoma, leiomyosarcoma, and hematologic malignancies. They are also seen as markers of neuromyotonia, Morvan's, epilepsy, limbic encephalits, and dysautonomia with hyperhidrosis and GI dysmotility. Animal passive transfer experiments suggest pathogenicitiy. IVIG and plasma exchange are beneficial.
Among 80 patients in this Mayo Clinic series, was usually an inflammatory or neurodegenerative disease. 11 were correctly thought to have autoimmune encephalopathy, 10 with CJD, 5 with viral encephalitis, 3 with recurrent TGA, 4 with psychiatric (anxiety disorder/panic attacks/ conversion disorder). Examination showed frontosubcortical involvement, pesonality change, executive dysfunction, disinhibition, visual hallucinations (10%), agitation or depression. Short term memory impairment, with 58 % having some form of seizure disorder (all types seen) . Cranial nerve involvement was seen in 19 % including diplopia (not MG associated), dysarthria, dysphagia, vision loss, hemifacial spasm, hyperphagia, hyponatremia, EPS, cerebellar ataxia, recurrent ON without NMO antibodies, myoclonus, hypersomnia, autonomic dysfunction. MRI's showed abnormalities in bilateral hippocampi, CN head, splenium , frontal lobe, or multifocal suspicious for CJD. MRI improved partly or wholly. SPECT, EEG, CSF generally or often abnormal. 47% had documented neoplasia, of whom 76 % were smokers, and VGKC preceded diagnosis by five or more months.
Coexisting antibodies included ANNA-1, PCA2, amphiphysin IgG, CRMP 5 IgG with ultimate diagnosis of 5 small cell lung CA, three thymic CA, four prostate adenoCA, Becelllymphoma, CLL, mycosis fungoides, 3 head and neck CA, one colonic adenoca. There also were benign neoplasia including 5 pituitary adenoca, one adrenal, one colonic, one parathyroid, one renal oncocytoma, one gastric leiomyoma. Other AI disorders were Hashimoto titers in 15, endocrine pancreas in 8, and pernicious anemia. 89 % improved with treatment, half dramatically so, including 8 of 10 with initial misdiagnosis of CJD. These included six patients with increased 14,3,3 or NSE, 5 of whom improved remarkably.
Monday, May 12, 2008
Changing the trajectory of cognitive decline?
Albert, MS. Clinical implications of basic research. NEJM 2007; 357:502-503.
This brief article describes recent findings in mouse models of cognitive loss. An enriched environment, containing many objects a mouse can explore, enhances learning and memory. Hippocampal neurogenesis is increased but not olfactory bulb. A model described by Fischer et al (Nature 2007) correlates with histone acetylation. Histone deacetylase (HDAC) inhibitor injections also facilitates memory. Histone acetylation is associated with synaptic plasticity.
This brief article describes recent findings in mouse models of cognitive loss. An enriched environment, containing many objects a mouse can explore, enhances learning and memory. Hippocampal neurogenesis is increased but not olfactory bulb. A model described by Fischer et al (Nature 2007) correlates with histone acetylation. Histone deacetylase (HDAC) inhibitor injections also facilitates memory. Histone acetylation is associated with synaptic plasticity.
Saturday, February 09, 2008
Capgras syndrome and its relationship to neurodegenerative disease
Joseph KA. Arch Neurol 2007;64:1762-1766.
Capgras s is delusional belief that a person has been removed and replaced by an impostor (husband, wife, etc.) In a review of 57 instances (Mayo Minnesota) 38 had neurodegenerative disease usually Lewy body disease. 100 % of those with LBD had visual hallucinations too compared to only one with AD. In younger patients CS occurred in the context of paranoid schizophrenia, schizoaffective disorder, methamphetamine abuse, and immediately after massive infarctions not in any one distinctive area.
Capgras s is delusional belief that a person has been removed and replaced by an impostor (husband, wife, etc.) In a review of 57 instances (Mayo Minnesota) 38 had neurodegenerative disease usually Lewy body disease. 100 % of those with LBD had visual hallucinations too compared to only one with AD. In younger patients CS occurred in the context of paranoid schizophrenia, schizoaffective disorder, methamphetamine abuse, and immediately after massive infarctions not in any one distinctive area.
Antiinflammatories, APOE status and dementia risk
Szekely CA, Breitner JCS, Fitzpatrick AL et al. NSAID use and dementia risk in the cardiovascular health study. Role of APOE and NSAID type. Neurology 2008; 70:17-24.
3229 subjects aged 65+, free of dementia were analyzed. Use of NSAID's led to lower dementia risk (did not matter which AED). Acetominophen did not prevent dementia. Risk reduction was present only among subjects having an APOE4 allele . A contoversy exists regarding the use of particular NSAID's (ie ibuprofen but not naproxen due to AB 42 lowering effect) but there was not advantage seen in this study.
Blogger comment:
Back to screening first degree relatives of Alz patients to prevent their risk of developing disease and advising them. We have a rationale for measuring APOE status in these patients (which has been missing for 15 years). Mechanisms, counselling, etc. needs to be put into place first.
3229 subjects aged 65+, free of dementia were analyzed. Use of NSAID's led to lower dementia risk (did not matter which AED). Acetominophen did not prevent dementia. Risk reduction was present only among subjects having an APOE4 allele . A contoversy exists regarding the use of particular NSAID's (ie ibuprofen but not naproxen due to AB 42 lowering effect) but there was not advantage seen in this study.
Blogger comment:
Back to screening first degree relatives of Alz patients to prevent their risk of developing disease and advising them. We have a rationale for measuring APOE status in these patients (which has been missing for 15 years). Mechanisms, counselling, etc. needs to be put into place first.
Sunday, February 03, 2008
The natural history of cognitive dysfunction in late onset GM2 gangliosidosis
Frey LC, Ringel SP, Filley CM. Arch Neurol 2005;62:989-994
Comment-- As one my mentors warned, pediatric diseases show up in adults and we need to diagnose them. This is the "adult form" of Tay Sachs disease. Late onset GM2 gangliosidosis (LGG)has late onset (adolescents and young adults), has a prolonged disease course, comparably late onset of neurologic dysfunction, and affects a significant minority of patients who are not of Ashkenazi Jewish descent.
Case one was a 46 year old Ahkenazi Jewish woman who had required special tutoring and was "emotionally immature." She showed emotional lability, aggressiveness and visual hallucinations. She had dysarthria, poor recall on memory tests, muscle atrophy and fasciculations, appendicular ataxia, and dysmetria, diffusely brisk reflexes and upgoing toes. EMG/ muscle biopsy done at age 13 showed diffuse denervation. She had a FSIQ of 93 at age 10, and 70 at age 20. CT showed cerebellar atrophy. Hex A level at age 20 showed partial deficiency (20.3 % residual WBC hex A).
Case 2 was sister of case one. She was learning disabled, weakness and ataxia, multiple psychiatric hospitalizations for psychoses, responsive to phenothiazines and lithium. She had partial hex A deficiency (20 %). She had supranuclear gaze palsy, tongue fasciculations, diffuse weakness, brisk reflexes, and flexor plantar responses. She had abnormal executive function, as detailed in Trailmaking Tests A and B and memory.
Case 3 was a 30 yo woman who had come to attention with deteriorating schoolwork in second grade. At age 25 she had a confusional state and profound abulia. She was briefly given AED's. MMSE was 27/30. She had limited upgaze, mild neck flexor weakness, diffuse limb weakness, brisk reflexes with bilateral Babinski signs, mild CT atrophy, slow RAM's, EMG showed abnormal spontaneous activity and decreased motor unit amplitude.
Review of 62 patients-- 2/3 were Ashknenazi Jews, 82 % LMN signs, and 69 % cerebellar signs, were seen. Mean hex A ranged from 0-48 %. 44 % were described as having cognitive dysfunction. 38 % of patients were cognitively stable, and 62 % had progressive cognitive loss.
Comment-- As one my mentors warned, pediatric diseases show up in adults and we need to diagnose them. This is the "adult form" of Tay Sachs disease. Late onset GM2 gangliosidosis (LGG)has late onset (adolescents and young adults), has a prolonged disease course, comparably late onset of neurologic dysfunction, and affects a significant minority of patients who are not of Ashkenazi Jewish descent.
Case one was a 46 year old Ahkenazi Jewish woman who had required special tutoring and was "emotionally immature." She showed emotional lability, aggressiveness and visual hallucinations. She had dysarthria, poor recall on memory tests, muscle atrophy and fasciculations, appendicular ataxia, and dysmetria, diffusely brisk reflexes and upgoing toes. EMG/ muscle biopsy done at age 13 showed diffuse denervation. She had a FSIQ of 93 at age 10, and 70 at age 20. CT showed cerebellar atrophy. Hex A level at age 20 showed partial deficiency (20.3 % residual WBC hex A).
Case 2 was sister of case one. She was learning disabled, weakness and ataxia, multiple psychiatric hospitalizations for psychoses, responsive to phenothiazines and lithium. She had partial hex A deficiency (20 %). She had supranuclear gaze palsy, tongue fasciculations, diffuse weakness, brisk reflexes, and flexor plantar responses. She had abnormal executive function, as detailed in Trailmaking Tests A and B and memory.
Case 3 was a 30 yo woman who had come to attention with deteriorating schoolwork in second grade. At age 25 she had a confusional state and profound abulia. She was briefly given AED's. MMSE was 27/30. She had limited upgaze, mild neck flexor weakness, diffuse limb weakness, brisk reflexes with bilateral Babinski signs, mild CT atrophy, slow RAM's, EMG showed abnormal spontaneous activity and decreased motor unit amplitude.
Review of 62 patients-- 2/3 were Ashknenazi Jews, 82 % LMN signs, and 69 % cerebellar signs, were seen. Mean hex A ranged from 0-48 %. 44 % were described as having cognitive dysfunction. 38 % of patients were cognitively stable, and 62 % had progressive cognitive loss.
Cognitive impairment in familial ALS
Wheaton MW, Salamone AR, Mosnik DM et al. Cognitive impairment in familial ALS. Neurology 2007; 69:1411-1417.
Background. 51 % of patients with sALS have mild cognitive impairment, esp. executive function and memory. A subset, 15 % have more sever impairments with features of FTD. Over 60 % of patients had some cognitive impairment, either moderate or severe, generally unrelated to motor variables.
Background. 51 % of patients with sALS have mild cognitive impairment, esp. executive function and memory. A subset, 15 % have more sever impairments with features of FTD. Over 60 % of patients had some cognitive impairment, either moderate or severe, generally unrelated to motor variables.
Binge eating in FTLD
Neurology 2007; 69: 1424-33 and editorial 1389-1390. Article by Wooley et al, editorial by Murray Grossman
FTLD patients binge eat, especially sweets, even when stated that they are full. Investigators found significant atrophy in ventral insula, rostral orbital frontal, and striatum of right hemisphere among six binge eaters. Interestingly other frontal lobe abnormalities on neuropsychological tests were not found. Also they did not gain weight, leading Grossman to question whether the eating was a form of L'Hermitte's environmental dependency.
FTLD patients binge eat, especially sweets, even when stated that they are full. Investigators found significant atrophy in ventral insula, rostral orbital frontal, and striatum of right hemisphere among six binge eaters. Interestingly other frontal lobe abnormalities on neuropsychological tests were not found. Also they did not gain weight, leading Grossman to question whether the eating was a form of L'Hermitte's environmental dependency.
Subscribe to:
Posts (Atom)