Table 1.
Generation of an “Infection Hypothesis” for idiopathic parkinsonism (IP), implicating the gut
| Year | Statistical model | Findings |
|---|---|---|
| 1992 [61] | Observational comparison nocturnal axial rotation in elderly IP probands, their spouses and control couples. | Rotation in spouses less than in controls, greater than in probands. a |
| 1993/4/6 [62, 63, 64] | Comparison measured facets of parkinsonism in elderly probands, their spouses, control couples. | Spouses significantly different from controls (toward parkinsonism) in measures of brady/hypokinesia, postural abnormality, rigidity, and frequency of seborrheic dermatitis. |
| 1997/8 [16, 65, 66] | Relationship serum immunoglobulin concentrations to presence/ absence of (i) Diagnosed IP, (ii) A parkinsonian feature in subjects without diagnosed parkinsonism, (iii) Specified medication in IP probands. | (i) No overall difference in IgM, A, or G with IP. b (ii) In controls, bradykinesia associated with higher IgA and lower M, postural abnormality with higher IgA, as if exaggerated ageing. (iii) IgA higher in probands with constipation warranting laxatives or taking antimuscarinic c . Higher IgA in ii and iii explained by A1 subclass: a systemic rather than mucosal response. |
| 1997/8 [16, 57] | (i) Comparison between IP probands and controls of current and estimated past frequency of defecation. (ii) Association serum IgA with a discriminant index for presence/ absence parkinsonism based on current bowel habit. (iii) Relative effect of tobacco smoking on bowel habit. | (i) Frequency less in probands prodromally (from fourth decade of life). (ii) IgA increased with index irrespective of subject group. (iii) Differential effect of smoking on “difficulty passing a motion”: laxative‐like effect greater in controls. |
| 1998 [56] | Comparison serum cortisol in IP probands and controls, taking into account: (i) Current or past smoking, (ii) Anti‐parkinsonian medication and laxatives in IP. | Cortisol higher in IP. In controls, the lower the cortisol, the shorter the stride and the more the deterioration over 4 years: relationship inverted in IP. (i) Smoking tended to be associated with lower cortisol, irrespective of group. (ii) Levodopa and dopaminergic agonists did not affect cortisol; selegiline and antimuscarinics d reduced it, constipation warranting laxatives tended to increase it. |
| 1999 [60] | Comparison serum IL‐6 and TNF‐α in IP probands and controls. | IL‐6 increased with age, effect of IP equivalent to more than 10 years of ageing. TNF‐α increased with age, not IP. Elevated in probands with impaired postural and psychomotor responses, suppressed with normal responses, in contrast to lack of performance relationship in controls. e |
a
No correlation between partners, effect independent of bed sharing.
b
Lymphopenia [23, 26] in IP may abrogate any overall difference in immunoglobulins present in prodrome. Higher IgA in IP with constipation likely to reflect small‐intestinal bacterial overgrowth.
c
Constipation is dose‐related adverse effect.
d
Paradoxical decrease with antimuscarinics explained by central cholingeric effects.
e
Differences in inflammatory response may determine predominant facets between and within individual(s). TNF‐α, tumor necrosis factor alpha; IL‐6, interleukin‐6.