Allostatic load and mental health during COVID-19: The moderating role of neuroticism.

BACKGROUND: During the COVID-19 pandemic increased risk of poor mental health has been evident across different cultures and contexts. This study aims to examine whether allostatic load (AL) prior to the pandemic was predictive of poor mental health during the pandemic, and if any associations were moderated by neuroticism. METHODS: Data were extracted from Waves 2 (2011, allostatic load), 3 (2012, neuroticism), and the COVID-19 study (April 2020) of the Understanding Society database in the UK; data were available for 956 participants. RESULTS: Mental health increased from 2012- to during the pandemic. Neuroticism and AL were positively associated with poorer mental health during COVID-19, such that those who had scored higher on neuroticism and had higher AL prior to the pandemic reported poorer mental health during the pandemic. Neuroticism was also a significant moderator; the effect of AL on mental health during the pandemic was exacerbated in those with high and moderate levels of neuroticism but not lower. Moreover, this was driven by the immune-related indices of AL. This withstood adjustment for age, gender, employment status and prior mental health. These findings are discussed in relation to the pathophysiological mechanisms of mental health.

Pergolide use in Parkinson disease is associated with cardiac valve regurgitation.

OBJECTIVE: To determine if pergolide injures heart valves, by comparing echocardiographic findings in pergolide-treated patients with those of a historical control group. METHODS: Letters were sent to all patients in the authors' practice believed to be taking pergolide, and those responders who wished to continue it were urged to undergo echocardiography. Echocardiograms were obtained on 46 patients, and scores for valvular regurgitation were compared with those from an age-matched control group derived from the Framingham Study. The composite valve regurgitation score was modeled as a linear function of total milligrams lifetime use of pergolide, controlling for age. RESULTS: Eighty-nine percent of pergolide-treated patients had some degree of valvular insufficiency. For each of the three valves for which there are control data, we found an approximately 2- to 3-fold increased risk of abnormal valves in the pergolide patients (odds ratio [OR] approximately 3) and an estimated 14-fold increased risk of concerning tricuspid regurgitation (OR = 18.4). The composite valve score (the sum of valve scores for each of the four valves) was a function of lifetime pergolide use. CONCLUSION: Pergolide may injure cardiac valves, resulting most commonly in tricuspid regurgitation.

Accuracy of clinical detection of INO in MS: corroboration with quantitative infrared oculography.

The authors compared the accuracy of clinical detection (by 279 physician observers) of internuclear ophthalmoparesis (INO) with that of quantitative infrared oculography. For the patients with mild adduction slowing, INO was not identified by 71%. Intermediate dysconjugacy was not detected by 25% of the evaluators. In the most severe cases, INO was not identified by only 6%. Oculographic techniques significantly enhance the precision of INO detection compared to the clinical exam.

Quantitative oculographic characterisation of internuclear ophthalmoparesis in multiple sclerosis: the versional dysconjugacy index Z score.

BACKGROUND: There is a poor correlation between multiple sclerosis disease activity, as measured by magnetic resonance imaging, and clinical disability. OBJECTIVE: To establish oculographic criteria for the diagnosis and severity of internuclear ophthalmoparesis (INO), so that future studies can link the severity of ocular dysconjugacy with neuroradiological abnormalities within the dorsomedial brain stem tegmentum. METHODS: The study involved 58 patients with multiple sclerosis and chronic INO and 40 normal subjects. Two dimensional infrared oculography was used to derive the versional dysconjugacy index (VDI)-the ratio of abducting to adducting eye movements for peak velocity and acceleration. Diagnostic criteria for the diagnosis and severity of INO were derived using a Z score and histogram analysis, which allowed comparisons of the VDI from multiple sclerosis patients and from a control population. RESULTS: For a given saccade, the VDI was typically higher for acceleration v velocity, whereas the Z scores for velocity measures were always higher than values derived from comparable acceleration VDI measures; this was related to the greater variability of acceleration measures. Thus velocity was a more reliable measure from which to determine Z scores and thereby the criteria for INO and its level of severity. The mean (SD) value of the VDI velocity derived from 40 control subjects was 0.922 (0.072). The highest VDI for velocity from a normal control subject was 1.09, which was 2.33 SD above the normal control mean VDI. We therefore chose 2 SD beyond this value (that is, a Z score of 4.33) as the minimum criterion for the oculographic confirmation of INO. Of patients thought to have unilateral INO on clinical grounds, 70% (16/23) were found to have bilateral INO on oculographic assessment. CONCLUSIONS: INO can be confirmed and characterised by level of severity using Z score analysis of quantitative oculography. Such assessments may be useful for linking the level of severity of a specific clinical disability with neuroradiological measures of brain tissue pathology in multiple sclerosis.

Proprioception in Parkinson's disease is acutely depressed by dopaminergic medications.

OBJECTIVES: Impaired proprioception has been previously reported in patients with Parkinson's disease. It was hypothesised that dopaminergic medications transiently depress proprioception, with amplification of adventitious movements as a result. This study tested for effects on proprioception of dopaminergic drugs, and for associations between such effects and drug induced dyskinesias. METHODS: In 17 patients with Parkinson's disease, arm proprioception was tested in the practically defined "off" state, and retested 1 hour after taking levodopa or dopamine agonist. Testing consisted of side to side comparison of elbow angle, matching the contralateral elbow angle, and spatial recall of an unrestrained arm. RESULTS: Proprioception deteriorated as hypothesised, reaching significance by one tailed t test for each of the three tasks. The relative deterioration (and the 95% lower confidence bound for estimated deterioration) was 31% (4%) for side to side elbow comparison, was 27% (11%) for accuracy in matching the contralateral elbow angle, and was 11% (0%) for spatial recall. Dyskinetic (n=6) and non-dyskinetic (n=11) patients did not differ significantly in these effects on proprioception. Control subjects (n=6) and untreated parkinsonian subjects (n=5) did not significantly differ from the parkinsonian patients in the off state. CONCLUSIONS: Administration of levodopa and dopamine agonists were associated with a modest acute suppression in central responsiveness to joint position. It is speculated that compensatory exaggerated movement could account in part for the phenomenon of drug induced dyskinesias.

Validation for tremor quantification of an electromagnetic tracking device.

An electromagnetic tracking system was used to record arm motion in subjects with Parkinson's disease (n = 23), essential tremor (n = 28) or without neurological disease (n = 4). Tremor magnitude was calculated by averaging the three-dimensional displacement of individual tremor bursts. Tremor magnitude calculated in this manner was quite closely correlated with a clinician's estimate (r = 0.88 and 0.86 for Parkinsonian and essential tremors, respectively) and was reproducible (r = 0.93 for repeated recordings). The accuracy of the device and algorithm was confirmed by mechanically generating oscillations of known magnitudes and frequencies. This device is adaptable for quantifying different types of tremors and its accuracy is easy to verify. Because position rather than acceleration is tracked, tremor amplitude can be stated in readily comprehensible units.

Spinocerebellar ataxia type 3 phenotypically resembling parkinson disease in a black family.

BACKGROUND: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), can present with parkinsonism. However, classically, atypical features, including pyramidal and cerebellar signs, peripheral neuropathy, and/or anterior horn cell dysfunction, are also seen. Levodopa responsiveness is unusual in this disorder. OBJECTIVE: To determine the cause of apparent parkinsonism suggestive of Parkinson disease (PD) in a large family of African origin. METHODS: We studied a large family in which apparent autosomal dominant parkinsonism suggestive of PD occurs in order to find the causal genetic mutation. Affected and unaffected family members were screened for the presence of a pathogenic expansion at the MJD/SCA3 locus using a polymerase chain reaction polyacrylamide gel electrophoresis-based assay. RESULTS: Three of the 4 individuals who were examined have a phenotype reminiscent of PD. Specifically, they have at least 2 of the cardinal features, are levodopa responsive, and have no atypical features. All affected family members were shown to possess pathogenic expansions in the MJD/SCA3 gene. CONCLUSIONS: Parkinsonism suggestive of PD due to MJD/SCA3 has not been previously reported, to our knowledge. However, atypical, though also levodopa-responsive, parkinsonism has been previously reported to occur in African American families, suggesting that that this phenotype is associated with African ancestry. In this regard, it is perhaps significant that all the individuals with parkinsonism have relatively low numbers of repeats (normal, 16-34; pathologic, 60-84). In families in which linkage analysis is being performed to determine a locus for autosomal dominant parkinsonism suggestive of PD, evaluation for the MJD/SCA3 mutation is indicated.

Questionnaire-based assessment of bladder dysfunction in patients with mild to moderate Parkinson's disease.

OBJECTIVES: To assess the lower urinary tract symptoms (LUTS) in men and women with mild to moderate Parkinson's disease (PD) using validated symptom questionnaires. METHODS: Eighty men and 39 women with mild to moderate PD (Hoehn and Yahr score less than 3) were mailed LUTS questionnaires to complete and return. Men received the American Urological Association Symptom Index and women received the Urogenital Distress Inventory-6. Patients not responding by mail were called and asked to complete the survey over the telephone. Control populations of both symptomatic and asymptomatic men and women (without PD) were identified for comparison. RESULTS: The overall response rate was 78%. Men with early-stage PD had higher American Urological Association Symptom Index scores than age-matched controls (total score of 12.0 versus 7.7, P <0.05) and scores similar to those reported for men with symptomatic benign prostatic hyperplasia (12.5). Specific items noted to be higher among the men with PD included questions regarding frequency and urgency. Women with PD had higher scores on the Urogenital Distress Inventory-6 than non-age-matched controls (total score of 4.8 versus 2.1, P <0.05), but lower scores than an age-matched group of neurologically intact women presenting for urologic evaluation of LUTS (6.9, P <0.05). CONCLUSIONS: On the basis of the responses to the validated symptom indexes, the development of LUTS appears to occur at an earlier stage of PD than was once appreciated. Prompt evaluation and treatment of patients with lower urinary tract complaints in the setting of PD may identify bladder dysfunction at an earlier, more treatable stage.

Cortical potentials at the frequency of absolute wrist velocity become phase-locked during slow sinusoidal tracking movements.

A 1-Hz rhythmic event-related potential was recorded at the scalp during performance of a 0.5-Hz tracking task. At cortical motor areas, negative peaks occurred 10-20 ms after peak tracking speeds. Analysis of single sweeps suggested that EEG phase was reset at initiation of the tracking motion and then maintained a constant relationship to wrist speed until task completion. Frequency analysis indicated that rhythm appearance in the averaged potential was predominantly due to phase-locking, because there was no tracking-related increase in 1 Hz amplitude within individual sweeps. While tracking, phase-locking was present over bilateral parieto-occipital and frontal regions, with a slight predominance at the contralateral frontal region. When subjects observed the target motion, phase-locking was localized to parieto-occipital regions. We suggest mental processes such as visual processing, visuomotor coordination and real-time motor planning are reflected in the pacing of localized cortical potential fluctuations.

Time-frequency analysis of tremors.

Time-frequency analysis methods were applied to surface EMG records of patients with tremor. Variation in tremor frequency over time and between muscles was measured in subjects with Parkinson's disease (n = 20), essential tremor (n = 8) and psychogenic tremor (n = 7). The effect of externally paced voluntary contractions on tremor frequency was also characterized. Psychogenic tremor involved fewer limbs and fewer limb segments than Parkinson's disease rest tremor and essential tremor, and its frequency was less consistent. In all subject groups, muscles within a single extremity generally had identical instantaneous frequencies. Frequency dissociation, used here to describe a modal contemporaneous frequency difference of more than 0.1 Hz between two extremities, was demonstrated for symptomatic tremors in 17 subjects with Parkinson's disease, in four subjects with essential tremor and in none of the subjects with psychogenic tremor. Dissociation between tapping and tremor limbs was demonstrated in an additional two subjects with Parkinson's disease and in all four remaining essential tremor subjects but in none of the psychogenic tremor subjects. Tremor maintained a different frequency from the tapping limb in Parkinson's disease and essential tremor, and its frequency in many cases shifted by at least 0.3 Hz compared with the non-tapping condition. For example, arm and leg tremors at 5.2 and 3.8 Hz, respectively, shifted to a common frequency of 4.6 Hz in one Parkinson's disease patient while using the contralateral arm to perform a tapping movement in time with a metronome at 2 Hz. These observations suggest the existence of distinct oscillator systems projecting to each tremoring limb, which can be linked to a variable degree, and which can be modulated by voluntary activation of another limb. Psychogenic tremor was not maintained while tapping with the contralateral arm: tremor either dissipated or shifted to the metronome's frequency. The latter response was also seen in normal volunteers mimicking tremor, but not in Parkinson's disease or essential tremor. We suggest that maintenance of phasic contraction in psychogenic tremor is not due to intrinsic instability of the motor system and that muscle activation in involved limbs may instead be synchronized to a common oscillator. As in voluntary movements, only a single rhythm may be easily followed at a time. Coexistence of muscle groups phasically contracting at consistently different instantaneous frequencies is evidence against a psychogenic aetiology of tremor.

Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates.

Autonomic dysfunction is a recognized feature of the Lambert-Eaton myasthenic syndrome (LES). However, the characteristic pattern of dysautonomia has not been clearly documented and its pathophysiologic basis is not known. We therefore abstracted autonomic symptomatology and results of quantitative tests for salivation, and vasomotor, cardiovagal, and sudomotor reflexes from records of 30 LES patients. Dry mouth (77%) and impotence (45% of men) were the most common symptoms. Composite Autonomic Scoring Scale results were abnormal in 93% of patients, and autonomic failure was severe in 20%. The frequency of specific test abnormalities were the following: sudomotor function, 83%; cardiovagal reflexes, 75%; salivation, 44%; and adrenergic function, 37%. Although voltage-gated N-type calcium (Ca2+) channels are implicated in autonomic transmission, the low frequency of serum antibodies to N-type Ca2+ channels found in the patients of this study (31% positive) argues against a pathogenic role in mediating LES-related dysautonomia. In contrast, 93% of the patients were seropositive for P/Q-type Ca2+ channel antibodies. A subset of these antibodies is thought to impair neuromuscular transmission. Autoantibodies of thyrogastric or glutamic acid decarboxylase specificity (markers of predisposition to type 1 diabetes mellitus) were found in 45% of patients, and type 1 antineuronal nuclear antibody (or anti-Hu, a marker of autoimmune neuropathy associated with small-cell lung carcinoma) was found in 3%. No autoantibody correlated with autonomic dysfunction severity. Sensorimotor neuropathy was documented in five patients, and was not significantly associated with autonomic neuropathy. Autonomic failure was most severe in older subjects with cancer (p = 0.02, age by cancer interaction).

Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes.

BACKGROUND: Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert-Eaton syndrome. The calcium-channel subtype that is responsible is not known. METHODS: We compared the effects of antagonists of L-type, N-type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. RESULTS: P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small-cell carcinoma cell lines. Anti-P/Q-type calcium-channel antibodies were found in serum from all 32 patients with Lambert-Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with Lambert-Eaton syndrome without cancer. Anti-N-type calcium-channel antibodies were found in 49 percent of the 65 patients with the Lambert-Eaton Syndrome. Lower titers of anti-P/Q-type and anti-N-type calcium-channel antibodies were found in 54 percent of 70 patients with a paraneoplastic encephalomyeloneuropathic complication of lung, ovarian, or breast carcinoma, 24 percent of 90 patients with cancer but no evident neurologic complications, 23 percent of 78 patients with sporadic amyotrophic lateral sclerosis, and less than 3 percent of 69 patients with myasthenia gravis, epilepsy, or scleroderma. CONCLUSIONS: The high frequency of P/Q-type calcium-channel antibodies found in patients with Lambert-Eaton syndrome implies that antibodies of this specificity have a role in the presynaptic pathophysiology of this disorder.