Balance in multiple sclerosis: relationship to central brain regions.

Dizziness, postural instability, and ataxia are among the most debilitating symptoms of multiple sclerosis (MS), reflecting, in large part, dysfunctional integration of visual, somatosensory, and vestibular sensory cues. However, the role of MS-related supratentorial lesions in producing such symptoms is poorly understood. In this study, motor control test (MCT) and dynamic sensory organization test (SOT) scores of 58 MS patients were compared to those of 72 healthy controls; correlations were determined between the MS scores of 49 patients and lesion volumes within 26 brain regions. Depending upon platform excursion direction and magnitude, MCT latencies, which were longer in MS patients than controls (p < 0.0001), were correlated with lesion volumes in the cortex, medial frontal lobes, temporal lobes, and parietal opercula (r's ranging from 0.20 to 0.39). SOT test scores were also impacted by MS and correlated with lesions in these same brain regions as well as within the superior frontal lobe (r's ranging from - 0.28 to - 0.40). The strongest and most consistent correlations occurred for the most challenging tasks in which incongruent visual and proprioceptive feedback were given. This study demonstrates that supratentorial lesion volumes are associated with quantitative balance measures in MS, in accord with the concept that balance relies upon highly convergent and multimodal neural pathways involving the skin, muscles, joints, eyes, and vestibular system.

Estrogen replacement therapy induces functional asymmetry on an odor memory/discrimination test.

The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 post-menopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination test. Similar laterality effects were not observed for an odor detection threshold test employing phenyl ethyl alcohol. These results suggest that estrogen influences the lateralization of an odor memory/discrimination task and that hormone replacement therapy in the menopause may be an excellent paradigm for understanding lateralizing effects of hormones on some sensory processes.

Accuracy of self-report in detecting taste dysfunction.

OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive value of responses to the following questionnaire statements in detecting taste loss: "I can detect salt in chips, pretzels, or salted nuts," "I can detect sourness in vinegar, pickles, or lemon," "I can detect sweetness in soda, cookies, or ice cream," and "I can detect bitterness, in coffee, beer, or tonic water." Responses to an additional item, "I can detect chocolate in cocoa, cake or candy," was examined to determine whether patients clearly differentiate between taste loss and flavor loss secondary to olfactory dysfunction. METHODS: A total of 469 patients (207 men, mean age = 54 years, standard deviation = 15 years; and 262 women, mean age = 54 years, standard deviation = 14 years) were administered a questionnaire containing these questions with the response categories of "easily," "somewhat," and "not at all," followed by a comprehensive taste and smell test battery. RESULTS: The questionnaire items poorly detected bona fide taste problems. However, they were sensitive in detecting persons without such problems (i.e., they exhibited low positive but high negative predictive value). Dysfunction categories of the University of Pennsylvania Smell Identification Test (UPSIT) were not meaningfully related to subjects' responses to the questionnaire statements. Both sex and age influenced performance on most of the taste tests, with older persons performing more poorly than younger ones and women typically outperforming men. CONCLUSION: Although it is commonly assumed that straight-forward questions concerning taste may be useful in detecting taste disorders, this study suggests this is not the case. However, patients who specifically report having no problems with taste perception usually do not exhibit taste dysfunction. The difficulty in detecting true taste problems by focused questionnaire items likely reflects a combination of factors. These include the relatively low prevalence of taste deficits in the general population and the tendency of patients to confuse loss of olfaction-related flavor sensations with taste-bud mediated deficits.

Influences of temporal lobe epilepsy and temporal lobe resection on olfaction.

Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR on olfaction using three well-validated olfactory tests and measuring  the tests' associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study.

Unilateral olfactory sensitivity in multiple sclerosis.

It is not known whether lateralized olfactory sensitivity deficits are present in MS. Since projections from the olfactory bulb to the olfactory cortex are largely ipsilateral, and since both functional imaging and psychophysical studies suggest that the right side of the brain may be more involved in olfactory processing than the left, we addressed this issue by administering well-validated tests of odor detection, along with tests of odor identification, to each side of the nose of 73 MS patients and 73 age-, gender-, and race-matched normal controls. We also determined, in 63 of the MS patients, whether correlations were present between the olfactory test measures and MRI-determined lesions in brain regions ipsilateral and contralateral to the nose side that was tested. No significant left:right differences in either olfactory sensitivity or identification were present, although in both cases mean performance was lower in the MS than in the control subjects (ps<0.0001). Scores on the two sides of the nose were positively correlated with one another (threshold r=0.56, p<0.0001; Identification r=0.71, p<0.0001). The percent of MS patients whose bilateral test scores fell below the 10th percentile of controls did not differ between the odor identification and detection threshold tests. Both left and right odor identification and detection test scores were weakly correlated with lesion volumes in temporal and frontal lobe brain regions (r's<0.40). Our findings demonstrate that MS does not differentially influence odor perception on left and right sides of the nose, regardless of whether sensitivity or identification is being measured. They also indicate that tests of odor identification and detection are similarly influenced by MS and that such influences are associated with central brain lesions.

Taste dysfunction in multiple sclerosis.

Empirical studies of taste function in multiple sclerosis (MS) are rare. Moreover, a detailed assessment of whether quantitative measures of taste function correlate with the punctate and patchy myelin-related lesions found throughout the CNS of MS patients has not been made. We administered a 96-trial test of sweet (sucrose), sour (citric acid), bitter (caffeine) and salty (NaCl) taste perception to the left and right anterior (CN VII) and posterior (CN IX) tongue regions of 73 MS patients and 73 matched controls. The number and volume of lesions were assessed using quantitative MRI in 52 brain regions of 63 of the MS patients. Taste identification scores were significantly lower in the MS patients for sucrose (p = 0.0002), citric acid (p = 0.0001), caffeine (p = 0.0372) and NaCl (p = 0.0004) and were present in both anterior and posterior tongue regions. The percent of MS patients with identification scores falling below the 5th percentile of controls was 15.07 % for caffeine, 21.9 % for citric acid, 24.66 % for sucrose, and 31.50 % for NaCl. Such scores were inversely correlated with lesion volumes in the temporal, medial frontal, and superior frontal lobes, and with the number of lesions in the left and right superior frontal lobes, right anterior cingulate gyrus, and left parietal operculum. Regardless of the subject group, women outperformed men on the taste measures. These findings indicate that a sizable number of MS patients exhibit taste deficits that are associated with MS-related lesions throughout the brain.

Influences of hormone replacement therapy on olfactory and cognitive function in postmenopausal women.

Olfactory dysfunction can be an early sign of Alzheimer's disease. Since hormone replacement therapy (HRT) may protect against Alzheimer's disease in postmenopausal women, the question arises as to whether it also protects against olfactory dysfunction in such women. A total of three olfactory and 12 neurocognitive tests were administered to 432 healthy postmenopausal women with varied HRT histories. Serum levels of reproductive hormones were obtained for all subjects; APOE-ε4 haplotype was determined for 77 women. National Adult Reading Test and Odor Memory/Discrimination Test scores were positively influenced by HRT. Odor Identification and Odor Memory/Discrimination Test scores were lower for women who scored poorly on a delayed recall test, a surrogate for mild cognitive impairment. The Wechsler Adult Intelligence Scale, Revised, as a Neuropsychological Instrument Spatial Span Backwards Test scores were higher in women receiving estrogen and progestin HRT and directly correlated with serum testosterone levels, the latter implying a positive effect of testosterone on spatial memory. APOE-ε4 was associated with poorer odor threshold test scores. These data suggest that HRT positively influences a limited number of olfactory and cognitive measures during menopause.

Pure-tone auditory thresholds are not chronically elevated in multiple sclerosis.

Despite the fact that acute cases of multiple sclerosis (MS)-related pure-tone hearing loss have been reported in the literature, consensus is lacking as to the chronic influences of MS on pure-tone thresholds. Most studies examining such influences have been limited by small sample sizes, lack of statistical comparisons between patients and controls, and confounding of the hearing measure with influences from sex and age. To date, associations between pure-tone thresholds and central MS-related brain lesions have not been assessed. In this study, pure-tone thresholds ranging from 0.5 to 8 kHz were measured in 73 MS patients and 73 individually age- and gender-matched normal controls. In 63 MS patients, correlations were computed between the threshold values and MRI-determined lesion activity in 26 central brain regions. Although thresholds were strongly influenced by sex, age, and tonal frequency, no meaningful influences of MS were discerned. Moreover, no significant association between the threshold values and central MS-related lesion activity was evident in any brain region evaluated. This study, the largest on this topic to use carefully matched control subjects and the sole study to assess relationships between auditory thresholds and central MS-related lesions, strongly suggests that (a) MS is not chronically associated with pure-tone hearing loss and (b) pure-tone thresholds are unrelated to MS lesion activity in higher brain regions. These findings, along with general reports from the literature, support the concept that when MS-related hearing threshold deficits are found, they are episodic and primarily dependent on lesions within the eighth nerve or brainstem.

A double-blind study of the influences of eszopiclone on dysgeusia and taste function.

Taste disturbance is a common, but poorly understood, side effect of a large number of medications. This double-blind study examined the frequency, intensity, and quality of taste disturbances related to the widely used hypnotic sleep aid eszopiclone (ESZ; Lunesta, as well as their associations with age, sex, body mass index (BMI), time of day, phenyl thiocarbamide (PTC) taste sensitivity, and ESZ saliva and blood levels. Sixty six percent of 24 female subjects and 53% of 15 male subjects reported dysgeusic sensations, mostly bitter/metallic, during the drug administration (respective placebo figures 17% and 7%). No meaningful relationships were found between the frequency or the intensity of the sensations and age, BMI, or PTC taste sensitivity. Dysgeusia was more intense and longer lasting in women than in men, stronger in the morning than in the evening, and positively correlated with drug plasma and saliva levels. In women, intensity ratings decreased across treatment days. Taste test measures were marginally, at best, influenced by ESZ. This study demonstrates, for the first time, that the dysgeusia associated with ESZ is systemically influenced by a number of factors, including sex, time since drug administration, and both blood and saliva levels of the drug.

Sniff magnitude test: relationship to odor identification, detection, and memory tests in a clinic population.

Recently a novel measure of olfactory function, the Sniff Magnitude Test (SMT), was developed that relies on changes in inhalation in response to an odor. The relationship of this unique test to that of other olfactory tests has received little investigation. In this study, we assessed, in 132 patients presenting to a chemosensory disorders clinic, the relationship of SMT scores to those from 3 standardized psychophysical tests: the University of Pennsylvania Smell Identification Test (UPSIT), a phenyl ethyl alcohol odor detection threshold test, and a short-term odor memory/discrimination test. SMT scores were roughly related to olfactory dysfunction categories defined for the UPSIT and correlated moderately with the other tests. Malodors (1% and 3% methylthiobutyrate [MTB], 1% ethyl 3-mercaptoproprionate) exhibited stronger correlations than nonmalodors (3% phenyl ethyl alcohol [PEA], 3% amyl acetate, 3% n-butanol) and elicited greater sniff suppression. In a principal component analysis, the SMT measures loaded on components different from those of the other tests, which loaded on a separate component. Anticipatory responses (i.e., smaller sniffs) occurred across trials for the first malodor (1% MTB), but not for the first nonmalodor (3% PEA), that was encountered. These results, along with those of an earlier factor analysis, suggest that sniff magnitude is influenced by odorant quality and intensity, as well as by cognitive factors.