Benjamin H. Eidelman

Prevalence of bowel dysfunction in multiple sclerosis: A population survey

An unselected outpatient population of 280 individuals with multiple sclerosis was surveyed to determine the prevalence of bowel dysfunction and to define their characteristics and their relationship to the nongastrointestinal manifestations of the disease. Constipation was present in 43%, was similar in frequency in both sexes, and was more common in patients, regardless of degree of disability, than in a control population. Frequency of constipation also correlated with duration of disease and genitourinary symptoms but did not correlate with use of any medications in mildly disabled patients. Fecal incontinence had occurred at least once in the preceding 3 mo in 51% of patients and once per week or more frequently in 25% of patients who were questioned in more detail with a follow-up questionnaire. Correlations of fecal incontinence with disability, duration of disease, and presence of genitourinary symptoms were similar to constipation. The prevalence of bowel dysfunction (constipation and/or fecal incontinence) in the multiple sclerosis population was 68%, and this manifestation was common even in mildly disabled subjects. Bowel dysfunction can be a source of considerable ongoing social disability in patients with multiple sclerosis. Further studies are needed to characterize the pathophysiology of this common disorder so that effective therapeutic strategies can be identified.

Anorectal sensory and motor function in neurogenic fecal incontinence: Comparison between multiple sclerosis and diabetes mellitus

We measured anorectal sensory and motor function in 11 patients with multiple sclerosis and fecal incontinence, 11 continent patients with multiple sclerosis, 10 diabetics with fecal incontinence, and 12 healthy control subjects. The threshold volume at which patients with multiple sclerosis and fecal incontinence experienced rectal sensation was higher than that in healthy controls (42.7 +/- 6.2 mL vs. 13.3 +/- 2.8 mL; P less than 0.01) and was similar to that in incontinent diabetics (36.5 +/- 5.7 mL). Patients with multiple sclerosis and incontinent diabetics also showed increased thresholds of phasic external sphincter contraction compared with controls (P less than 0.05). Diabetics with incontinence had reduced resting and maximal voluntary anal sphincter pressures compared with controls (P less than 0.05), whereas patients with multiple sclerosis and incontinence showed only decreased maximal voluntary anal sphincter pressures (P less than 0.01 vs. controls and diabetics). Incontinent patients with multiple sclerosis also required smaller volumes of rectal distention to inhibit internal sphincter tone compared with diabetics and controls (P less than 0.01). Decreased maximal voluntary squeeze pressures were less severe in continent patients with multiple sclerosis than in incontinent patients with multiple sclerosis. We conclude that impaired function of the external anal sphincter and decreased volumes of rectal distention to inhibit the internal anal sphincter or both may contribute to fecal incontinence in multiple sclerosis. In addition, increased thresholds of conscious rectal sensation in some incontinent patients with multiple sclerosis and diabetes mellitus may contribute to fecal incontinence by impairing the recognition of impending defecation.

Prevalence of bowel dysfunction in multiple sclerosis

Abstract An unselected outpatient population of 280 individuals with multiple sclerosis was surveyed to determine the prevalence of bowel dysfunction and to define their characteristics and their relationship to the nongastrointestinal manifestations of the disease. Constipation was present in 43%, was similar in frequency in both sexes, and was more common in patients, regardless of degree of disability, than in a control population. Frequency of constipation also correlated with duration of disease and genitourinary symptoms but did not correlate with use of any medications in mildly disabled patients. Fecal incontinence had occurred at least once in the preceding 3 mo in 51% of patients and once per week or more frequently in 25% of patients who were questioned in more detail with a follow-up questionnaire. Correlations of fecal incontinence with disability, duration of disease, and presence of genitourinary symptoms were similar to constipation. The prevalence of bowel dysfunction (constipation and/or fecal incontinence) in the multiple sclerosis population was 68%, and this manifestation was common even in mildly disabled subjects. Bowel dysfunction can be a source of considerable ongoing social disability in patients with multiple sclerosis. Further studies are needed to characterize the pathophysiology of this common disorder so that effective therapeutic strategies can be identified.

Predicting outcome of relaxation therapy in headaches: The role of “depression”

This study evaluated whether improvement of headaches during relaxation therapy was related to pretreatment scores on tests measuring depression: the Beck Depression Inventory (BDI) and the depression scale of the MMPI. Seventeen patients were treated in eight 1-hour sessions of relaxation therapy. During treatment, there was a significant improvement of headache activity averaging a 34% decrease in pain with 24% much improved, 41% moderately improved, and 35% inimproved. Multiple regression analyses indicated that, controlling for differences in pretreatment pain levels, there were significant negative correlations between improvement and scores on the Beck, but not for scale 2 of the MMPI. For the BDI, a score of 8 or above predicted poor prognosis and a score of 3 or less predicted favorable prognosis.

Tc-99m hexamethylpropylene amine oxime scintigraphy in the diagnosis of Brain death and its implications for the harvesting of organs used for transplantation

PURPOSE Diagnosing brain death is important in managing the comatose patient for whom the continuation of life support is being questioned and when organ harvesting is being considered. The virtual immediate localization of Tc-99m HMPAO to cerebral and cerebellar tissue provides an index of blood perfusion, and its absence denotes brain death. Other methods for assessing brain death include cerebral angiography, MRI, CT imaging after inhalation of stable xenon, electroencephalography, and clinical examination. The contrast material used for angiography may damage harvested organs, and the other studies have significant errors. MRI, CT imaging, and angiography are unsuitable for bedside use. METHODS Twenty-three patients, who presented with head trauma, prolonged anoxia or intrinsic brain disease (e.g., glioblastoma multiforme) and who were brain-dead by clinical examination criteria, were referred to the nuclear medicine division for verification of brain death. For adults, approximately 25 mCi Tc-99m hexamethylpropylene amineoxime (HMPAO) was administered intravenously. All patients but one were imaged using a mobile scintillation camera at the bedside. RESULTS We demonstrated (1) both cerebral and cerebellar perfusion, (2) neither cerebral nor cerebellar perfusion, (3) cerebral without cerebellar perfusion, and (4) cerebellar without cerebral perfusion. Patients without cerebral perfusion were diagnosed as brain-dead. The significance of a viable cerebellum in the absence of cerebral viability was not fully appreciated, although organs were harvested from such patients. We determined how well the clinical examination criteria held up in the diagnosis of brain death against the new gold standard of Tc-99m HMPAO scintigraphy: Clinical examination criteria correctly predicted brain death only 83% of the time compared with HMPAO scintigraphy. CONCLUSIONS Brain death assessment by Tc-99m HM-PAO scintigraphy has proved to be a reliable, safe, and cost-effective bedside method and may have practical application in the assessment of brain death in potential cadaveric donors.

Nonpharmacological Treatment of Menstrual Headache: Relaxation-Biofeedback Behavior Therapy and Person-Centered Insight Therapy

SYNOPSIS

INFLUENCE OF FK 506 (TACROLIMUS) ON CIRCULATING CD4 + T CELLS EXPRESSING CD25 AND CD45RA ANTIGENS IN 19 PATIENTS WITH CHRONIC PROGRESSIVE MULTIPLE SCLEROSIS PARTICIPATING IN AN OPEN LABEL DRUG SAFETY TRIAL

We have taken the opportunity of a clinical trial of the potential efficacy and safety of FK 506 (tacrolimus) in chronic progressive multiple sclerosis (MS) to examine the influence of this potent new immunosuppressant on circulating T-lymphocytes in an otherwise healthy non-transplant population. Peripheral blood levels of subsets of CD4+ T lymphocytes expressing the activation molecule interleukin-2 receptor (p55 alpha chain; CD25) or the CD45RA isoform were determined sequentially in 19 patients that were treated continuously with oral FK 506 (starting dose 0.15 mg/kg/day) for 12 months. No significant change in the proportion of circulating CD25+ CD4+ cells was observed over the study period in which the mean trough plasma FK 506 level rose from 0.3 +/- 0.2 to 0.5 +/- 0.4 ng/ml. There was also no significant effect of FK 506 on the percentage of CD45R+ CD4+ cells in the peripheral blood at 12 months compared with pretreatment values. Analysis of a subgroup of 7 patients, who showed a sustained reduction in CD25+ CD4+ cells and a reciprocal increase in CD45RA+ CD4+ cells for at least 6 months after start of treatment, did not reveal any difference in disability at one year compared with the treatment group as a whole. The side effects of FK 506 were mild and the overall degree of disability estimated by the mean Kurtzke expanded disability status scale (EDSS) score or the ambulation index did not deteriorate significantly in the 19 patients studied over the 12 months of FK 506 administration.

Neurological Complications of Immunosuppressive Agents

The majority of immunosuppressive agents used to prevent rejection in organ transplant recipients are neurotoxic and can impact upon the function of structures throughout the nervous system. The clinical manifestations can be quite diverse.

Mechanisms of Cerebrovascular Dilation by Ether in Monkeys

We hypothesized that when the depth of ether anesthesia is increased from 2 to 5%, cerebral vessels dilate secondary to circulating catecholamine stimulation of cerebral metabolism. Cerebral blood flow (CBF) by 133Xe clearance and cerebral metabolic rate for oxygen (CMRO2) were measured on 2% and then 5% ether in air in two groups of seven monkeys each during mechanical ventilation. Propranolol, 0.5 mg/kg i. v., was infused over 5 min in one group, and the other received saline. All measurements were repeated on 5% and 2% ether. Cerebrovascular resistance (CVR) fell by 30%, from 2.28 2± 0.61 (mean ± SD) to 1.51± 0.28 mm Hg ml−1 100 g−1 min−1 (p < 0.01), with the increase in ether from 2 to 5%. CBF and CMRO2 were unaltered from values of about 45 ml 100 g−1 min−1 and 2.3 ml 100 g−1 min−1, respectively. During 5% ether anesthesia, propranolol had no effect on CBF, CMRO2, or CVR. On 2% ether, it increased CVR twofold, from 1.5 ± 0.30 to 3.0 ± 1.0 mm Hg ml−1 100 g−1 min−1, and decreased CBF by 33%, from 48 ± 8 to 32 ± 10 ml 100 g−1 min−1. Plasma epinephrine was twofold higher on 2% compared to 5% ether, both before and after saline or propranolol infusion. In monkeys, cerebrovascular dilation by ether at 5% compared to 2% is not secondary to catecholamine stimulation of CMRO2. It may result from a direct effect of either plasma catecholamines or ether on the cerebrovasculature.