Parkinson Disease: Ibrahim MA

Dobbs RJ, Dobbs SM, Weller C, Charlett A, Bjarnason IT, Curry A, Ellis DS, Ibrahim MA, McCrossan MV, O'Donohue J, Owen RJ, Oxlade NL, Price AB, Sanderson JD, Sudhanva M, Williams J. · Section of Clinical Neuropharmacology, Institute of Psychiatry, King's College London, London, UK. or · Helicobacter. · Pubmed #19250506 No free full text.

Abstract: We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.

Bjarnason IT, Bjarnason IT, Charlett A, Dobbs RJ, Dobbs SM, Ibrahim MA, Kerwin RW, Mahler RF, Oxlade NL, Peterson DW, Plant JM, Price AB, Weller C. · Section of Neuropharmacology, Institute of Psychiatry, London, UK. · Helicobacter. · Pubmed #16104943 No free full text.

Abstract: BACKGROUND: Links between etiology/pathogenesis of neuropsychiatric disease and infection are increasingly recognized. AIM: Proof-of-principle that infection contributes to idiopathic parkinsonism. METHODS: Randomized, double-blind, placebo-controlled efficacy study of proven Helicobacter pylori eradication on the time course of facets of parkinsonism. Intervention was 1 week's triple eradication therapy/placebos. Routine deblinding at 1 year (those still infected received open-active), with follow-up to 5 years post-eradication. Primary outcome was mean stride length at free-walking speed, sample size 56 for a difference, active vs. placebo, of 3/4 (between-subject standard deviation). Recruitment of subjects with idiopathic parkinsonism and H. pylori infection was stopped at 31, because of marked deterioration with eradication failure. Interim analysis was made in the 20 who had reached deblinding, seven of whom were receiving antiparkinsonian medication (long-t(1/2), evenly spaced) which remained unchanged. RESULTS: Improvement in stride-length, on active (n = 9) vs. placebo (11), exceeded size of effect on which the sample size was calculated when analyzed on intention-to-treat basis (p = .02), and on protocol analysis of six weekly assessments, including (p = .02) and excluding (p = .05) those on antiparkinsonian medication. Active eradication (blind or open) failed in 4/20, in whom B-lymphocyte count was lower. Their mean time course was: for stride-length, -243 (95% CI -427, -60) vs. 45 (-10, 100) mm/year in the remainder (p = .001); for the ratio, torque to extend to flex relaxed arm, 349 (146, 718) vs. 58 (27, 96)%/ year (p < .001); and for independently rated, visual-analog scale of stance-walk videos (worst-best per individual identical with 0-100 mm), -64 vs. -3 mm from anterior and -50 vs. 11 lateral (p = .004 and .02). CONCLUSIONS: Interim analysis points to a direct or surrogate (not necessarily unique) role of a particular infection in the pathogenesis of parkinsonism. With eradication failure, bolus release of antigen from killed bacteria could aggravate an effect of ongoing infection.

Hamad AI, Ibrahim MA, Sulaiti EM. · Department of Neurology, Hamad General Hospital, Doha, Qatar. · Saudi Med J. · Pubmed #14758386 No free full text.

Abstract: OBJECTIVE: Dementia is a major public health problem among the elderly in developed countries and a growing problem in the underdeveloped countries. There are no published data on dementia in any of the Arabic countries. The aim of this study was to determine the different sub-types of dementia among Qataris. METHODS: A retrospective and prospective ongoing hospital-based study in which all medical records of the patients with diagnosis of dementia seen at the Hamad General Hospital, Doha, Qatar, between June 1997 and June 2003, whether inpatient or outpatient were reviewed. Dementia was defined according to diagnostic and statistical manual (DSM) IV criteria. Those who had dementia were evaluated by a psychologist, psychiatrist, neurologist and a geriatrician. All had brain computerized tomography, magnetic resonance imaging or both and routine blood tests. Finally, they were classified into sub-types according to the cause of dementia. RESULTS: Out of 300 patients, 134 fulfilled the inclusion criteria, most of them were illiterate, married and non-smokers. Among those dementia sub-types were: Alzheimer disease (AD) 39 (29%), vascular dementia (VaD) 30 (22%), mixed AD and VaD 20 (15%) and Parkinson's disease with dementia 8 (6%) were noted. The rest of them had dementia due to other medical conditions. CONCLUSION: Our study showed that AD is more prevalent than VaD. It also showed that patients and their families seek medical help late due to the general belief among the public that forgetfulness and other associated cognitive impairment are part of the normal aging process. The emergence of new drugs and advancement in the prevention of cerebrovascular diseases makes early diagnosis of dementia sub-type important. A community based study, to show the real prevalence and incidence of sub-types of dementia, is highly indicated. These data are necessary for planning and setting up community services and health care programs for demented patients.