Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

Background: Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT. Discussion: Our case demonstrates multiple possible causes of cerebellar ataxia in a patient, including hypothyroidism, HT, chronic ET, and bilateral thalamic DBS. Counseling of patients may be appropriate when multiple risk factors for cerebellar ataxia coexist in one individual.</div

Association Between Pathology and Electroencephalographic Activity in Parkinson\u27s Disease

Introduction. The key mechanisms that connect Parkinson€™s disease pathology with dementia are unclear. We tested the hypothesis that the quantitative spectral electroencephalographic measure, delta bandpower, correlates with Lewy type synucleinopathy on pathological examination in Parkinson€™s disease. As a corollary hypothesis, we analyzed whether there would be delta bandpower electroencephalographic differences between Parkinson€™s disease dementia cases with and without pathological criteria for Alzheimer€™s disease. Methods. We used pathological examination results from 44 Parkinson€™s disease subjects from our brain bank with various degrees of cognitive decline, who had undergone electroencephalography. Pathological grading for Lewy type synucleinopathy, plaques, tangles, and indications of vascular pathology in subcortical and cortical areas were correlated with the most associated electroencephalographic biomarker with Parkinson€™s disease dementia in our laboratory, delta bandpower. Group differences for all spectral electroencephalographic measures were also analyzed between cases with and without pathological criteria for Alzheimer€™s disease. Results. Findings revealed significant correlations between delta bandpower with Lewy type synucleinopathy, whereas indications of Alzheimer€™s disease or vascular pathology had nonsignificant correlation. The strongest association was with delta bandpower and Lewy type synucleinopathy in the anterior cingulate region. Mean delta bandpower was higher in the group for Parkinson€™s disease dementia with Alzheimer€™s disease pathology criteria than without. Conclusions. Lewy type synucleinopathy severity appears to be more associated with increased delta bandpower than with Alzheimer€™s disease pathology or indications of vascular pathology over all cases. However, the presence of Alzheimer€™s pathology may associate with more cortex physiological disruption in a subset of cases

Olfaction in the elderly: A cross-sectional analysis comparing Parkinson\u27s disease with controls and other disorders

Olfactory dysfunction in Parkinson\u27s disease (PD) is an association that has been well documented in the medical literature, although the underlying pathophysiologic mechanism has not been clearly elucidated. In the Sun Health Research Institute Brain and Body Donation Program, subjects were tested for olfactory function. Olfaction was impaired in subjects with clinically probable PD but not those with essential tremor (ET), restless legs syndrome (RLS), or mild cognitive impairment. In the elderly control population there were no differences between genders and the UPSIT score decreased by 3.2 points per decade. These data confirm previous findings in PD, ET, and RLS, and expand the data for an elderly control population. © 2010 Informa Healthcare USA, Inc

Autonomic complaints in patients with restless legs syndrome

Background: Data regarding autonomic function in restless legs syndrome (RLS) are limited to heart rate and blood pressure changes in cases with periodic limb movements (PLMS). Methods: We compared autonomic symptoms of 49 subjects with RLS vs 291 control subjects using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire, consisting of 23 items in six domains scored from 0 to 3. The total score and domain scores were transformed to 0-100 points. Subjects with neurodegenerative disorders (i.e., dementia, Parkinsonism) were excluded. Results: The RLS group was younger (mean. ±. standard deviation, 77.9. ±. 8.0 vs 80.5. ±. 7.9. years; P=.03) and included more women (84% vs 69%; P=.04). The mean SCOPA-AUT total score was higher in the RLS group compared with the control group (20. ±. 11 vs 16. ±. 9; P=.005). Additionally the RLS group had abnormalities in gastrointestinal, cardiovascular, and pupillomotor domains. When comparing the percentage of subjects with any complaint on individual questions (score of ≥1), the RLS group had a greater number of subjects with sialorrhea, constipation, early abdominal fullness, lightheadedness when standing, and heat intolerance. Conclusions: Autonomic complaints, especially gastrointestinal, cardiovascular, and oversensitivity to light, were significantly increased in subjects with RLS. Causes for autonomic dysfunction in RLS require further investigation. © 2013 Elsevier B.V

Essential Tremor in the Elderly and Risk for Dementia

The objective is to examine the risk of dementia in subjects with essential tremor (ET) involved in the Arizona Study of Aging and Neurodegenerative Disorders. All subjects were free of a neurodegenerative diagnosis at baseline and had annual motor, general neurological, and neuropsychological assessments. Subjects with ET were compared with controls for the risk of dementia. There were 83 subjects with ET and 424 subjects without tremor. Mean age at study entry was 80 ± 5.9 for ET and 76 ± 8.5 for controls. Median tremor duration was 5.2 years at study entry. Followup was a median of 5.4 years (range 0.9 to 12.1). The hazard ratio for the association between ET and dementia was 0.79 (95% CI 0.33 to 1.85). The hazard ratio for the association between tremor onset at age 65 or over, versus onset before age 65, was 2.1 (95% CI 0.24 to 18) and the hazard ratio for the association between tremor duration greater than 5 years, versus less than 5 years, was 0.46 (95% CI 0.08 to 2.6). We conclude that all elderly ET was not associated with an increased risk of dementia but that a subset of subjects with older age onset/shorter duration tremor may be at higher risk

No evidence for cognitive dysfunction or depression in patients with mild restless legs syndrome

Restless legs syndrome is a common disoder that may interrupt sleep and has been reported to produce daytime fatigue and/or mood changes. This study assessed whether patients with RLS have more cognitive dysfunction and depression than individuals of the same age and education who do not have RLS. The study showed that older individuals with mild RLS for at least 1 year do not have cognitive dysfunction and are not depressed compared with a control group of similar age and education. © 2009 Movement Disorder Society

Concomitant pathologies among a spectrum of parkinsonian disorders

IntroductionMany clinicopathological studies do not specify the presence of other pathologies located within the brain, so disease heterogeneity may be under appreciated.ObjectiveThe purpose of this study was to determine the frequencies of concomitant pathologies among parkinsonian disorders.MethodsData from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), an ongoing longitudinal clinical-neuropathological study, was used to analyze concomitant pathologies, including Alzheimer's disease (AD), argyrophilic grains (Arg), cerebral amyloid angiopathy (CAA), cerebral white matter rarefaction (CWMR) and overlap of each parkinsonian disorder in clinico-pathologically defined Parkinson's disease (PD; N&nbsp;=&nbsp;140), dementia with Lewy bodies (DLB; N&nbsp;=&nbsp;90), progressive supranuclear palsy (PSP; N&nbsp;=&nbsp;64), multiple system atrophy (MSA; N&nbsp;=&nbsp;6), corticobasal degeneration (CBD; N&nbsp;=&nbsp;7); and normal elderly (controls; N&nbsp;=&nbsp;166).ResultsOf the neuropathologically-confirmed PD cases, 38% had a concomitant diagnosis of AD, 9% PSP, 25% Arg, 44% CWMR, and 24% CAA. For DLB, 89% had AD, 1% PSP, 21% Arg, 51% CWMR, and 50% CAA. For PSP cases, 36% had AD, 20% PD, 1% DLB, 44% Arg, 52% CWMR and 25% CAA. Similar heterogeneity was seen for MSA and CBD cases. Many cases had more than one of the above additional diagnoses.ConclusionsThese data demonstrate a great deal of concomitant pathologies among different types of parkinsonian disorders; this may help explain the heterogeneity of clinical findings

Longitudinal EEG changes correlate with cognitive measure deterioration in Parkinson\u27s disease

Background: QEEG could provide physiological biomarkers for changes over time in Parkinson\u27s disease (PD) cognitive decline if they track with longitudinal neuropsychological performance. Objective: Our aim was to correlate longitudinal changes in frequency domain quantitative electroencephalography (QEEG) measures with change in neuropsychological performance testing in PD. Methods: 71 PD subjects, not demented at baseline, were studied from the Arizona Study of Aging and Neurodegenerative Disorders cohort. Baseline and follow-up digital EEG from PD subjects were analyzed for QEEG measures of background rhythm frequency and global relative power in delta (2.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) bands. Baseline and subsequent evaluation included Mini Mental Status Examination and five other neuropsychological tests that load on cognitive domains known to decline in PD. Pearson coefficient was used to assess correlations. Multiple linear regression modeling was used to assess the effect of variable combinations of QEEG and other measures, including age and PD duration. Results: Changes in delta bandpower showed the highest and most consistent pattern of correlations with longitudinal changes in neuropsychological testing. The highest correlation was between delta bandpower increase and decline in the Rey Auditory-Verbal Learning Test (-0.59:p \u3c 0.001). Delta bandpower was also increased in the incident dementia group compared to non-dementia at followup. Conclusions: 1) Longitudinal change in the QEEG frequency domain measure of delta bandpower correlated best with longitudinal neuropsychological performance change in PD; 2) These results constitute preliminary evidence that delta bandpower may be a suitable biomarker for evaluating PD cognitive deterioration longitudinally

Unawareness of Hyposmia in Elderly People With and Without Parkinson\u27s Disease

Background: Hyposmia is common in Parkinson\u27s disease (PD) and is also observed with normal aging. It can be ascertained through objective testing, but it is unclear whether patients are aware of deficits and whether this has implications for cognitive status. Methods: Subjects in the Arizona Study of Aging and Neurodegenerative Disorders were studied with annual motor and cognitive testing with objective smell testing (University of Pennsylvania Smell Identification Test; UPSIT) done every third year beginning in 2002. Those with a baseline UPSIT \u3c25th percentile (hyposmia) were studied for presence of unawareness of hyposmia and cognitive status. Results: There were 75 subjects with PD and 143 nonparkinsonian controls with hyposmia. Lack of awareness of hyposmia was present in 16% of PD subjects and 47% of those without PD. In PD, there was no increase in unawareness in PD with dementia. In non-PD controls, unawareness was correlated with presence of dementia. Unawareness of hyposmia correlated most strongly with the neuropsychiatric tests of learning and memory. In controls without dementia or PD, 48% were unaware. Conclusions: Querying patients about anosmia might be useful in parkinsonian disorders without objective testing. However, in elderly controls, it should be followed by objective testing and lack of awareness has implications for worsened cognitive status