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.
Sunday, December 02, 2007
Dementia mimicking FTD with striatal hypermetabolic
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.
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.
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
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