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.

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.

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.

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.

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.