Olfactory dysfunction in essential tremor: a deficit unrelated to disease duration or severity

Because olfactory dysfunction is a feature of neurodegenerative diseases, the authors hypothesized that it would be present in essential tremor. Thirty-seven cases and control subjects underwent the University of Pennsylvania Smell Identification Test. Mean score was lower in cases than in control subjects (29.0 +/- 6.1 vs 31.9 +/- 4.6, p = 0.02) and was not correlated with tremor severity or duration.     

Assessment of general movements in relation to neurologic signs at age two years

Abnormal movement patterns during the fidgety period, as identified by Prechtl's method for qualitative assessment of general movements, and the presence of minor neurologic and cranial signs at age 2 years, as defined by Amiel-Tison, are related to minor developmental disorders. Our study analyzed the relationship between the two assessment methods in 45 preterm infants. Cerebral palsy was identified in 4, minimal cerebral palsy in 2, and the Amiel-Tison triad in 4 children; in all, continuously abnormal patterns of general movements were present. In the intermediate group with 2 signs of the triad, one child exhibited normal movements in the writhing period, and all were abnormal in the fidgety period. The intermediate group, with one sign of the triad, comprised 9 children: abnormal findings in the writhing period were present in 8, and in the fidgety period in 7. Among 16 children without neurologic signs, normal general movements were present in 7 children during the writhing period, and in 5 during the fidgety period. We confirmed good correlation between general movements and neurologic outcome at age 2 years (Pearson's R at term age, 0.51; at fidgety period, 0.62).     

Cerebellar dysfunction in neuroleptic naive schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs.

BACKGROUND: There is increasing evidence that, aside from motor coordination, the cerebellum also plays an important role in cognition and psychiatric disorders. Our previous studies support the hypothesis that cerebellar dysfunction may disrupt the cortico-cerebellar-thalamic-cortical circuit and, in turn, lead to cognitive dysmetria in schizophrenia. The goal of this study was to investigate cerebellar dysfunction in schizophrenia by examining the clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs in schizophrenia patients. METHODS: We compared the prevalence of cerebellar neurologic signs in 155 neuroleptic-naive schizophrenia patients against 155 age- and gender-matched healthy control subjects. Differences in clinical characteristics, standardized neuropsychologic performance, and magnetic resonance imaging brain volumes between patients with and without cerebellar signs were also examined. RESULTS: Patients had significantly higher rates of cerebellar signs than control subjects, with coordination of gait and stance being the most common abnormalities. Patients with lifetime alcohol abuse or dependence were no more likely than those without alcoholism to have cerebellar signs. Presence of cerebellar signs in patients was associated with poorer premorbid adjustment, more severe negative symptoms, poorer cognitive performance, and smaller cerebellar tissue volumes. CONCLUSIONS: These findings lend further support for cerebellar dysfunction in schizophrenia.     

Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier

A clinical association between Gaucher disease and parkinsonism has been demonstrated. We herein report a Japanese patient with type 3 Gaucher disease who was compound heterozygous for F213I and L444P mutations in the glucocerebrosidase gene while his father was heterozygous for the L444P mutation. They both presented with parkinsonism characterized by a predominance of akinetic-rigid signs and a favorable response to anti-Parkinson therapies. We investigated the dopaminergic neuronal function using positron emission tomography (PET) with radioligands, [(11)C] CFT and [(11)C] raclopride. PET studies of both patients demonstrated the [(11)C] CFT uptake to be severely decreased in the putamen and the caudate nucleus, however, the [(11)C] raclopride uptake was normal in the basal ganglia. Although the majority of Gaucher disease patients with parkinsonism tend to be refractory to anti-Parkinson therapies. The clinical features and the findings of the PET studies suggest that patients with parkinsonism associated with the mutation in the glucocerebrosidase gene, even in heterozygosis, may be related to the presynaptic dopaminergic neuronal dysfunction reported in Parkinson's disease. A PET study to evaluate the dopaminergic neuronal function in Gaucher disease would provide both a better understanding of the effects of anti-Parkinson therapies and a help to improve our ability to make an early diagnosis of parkinsonism associated with Gaucher disease.     

Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis

We reviewed the medical records of 821 Olmsted County residents who had suffered head trauma with presumed brain injury between 1935 and 1974 and were more than 40 years old at the time of their last medical assessment. These patients were followed over 15,000 person-years for dementia and other degenerative neurologic diseases. The standardized morbidity ratio (SMR) for dementia was 1.06, and the SMR for dementia of the Alzheimer type was 1.00. These values are not significantly elevated and are inconsistent with studies that suggest that head trauma is a risk factor for Alzheimer's disease. In addition, the SMRs for parkinsonism (1.04), Parkinson's disease (0.94), and amyotrophic lateral sclerosis (1.05) were not significantly elevated, providing no evidence that head trauma is a risk factor for these disorders. However, these latter results are based on smaller total case numbers.     

Perceptual motor dysfunction in Parkinson''s disease: a deficit in sequential and predictive voluntary movement.

We studied the ability of Parkinsonian patients and controls to generate voluntary movements on a tracing task. Subjects were videotaped while tracing designs of increasing complexity, presented on a vertical, transparent screen. Some designs were presented in a degraded form and subjects filled in their missing sections. Subjects also received a constructional task and a test of general intellectual ability. The quality of errors on the tracing task differed in the Parkinsonian and control groups. Parkinsonian patients made two distinct types of errors. One probably related to the motor disorders of the disease, but another seemed to be related to a higher level of control over sequential and predictive movements. The latter correlated with performance on the constructional and general intellectual tasks. These results suggest that Parkinson's disease may affect basal ganglia structures that are necessary for voluntary movements which require sequencing or planning. Clinically this may be observed in perceptual motor tasks since they require both voluntary movement and sequential organisation of behaviour.     

Effect of sulfamethoxazole and trimethoprim on neurologic dysfunction in a patient with Joseph's disease

Joseph's disease, an autosomal dominant, degenerative neurologic disease found in the Portuguese, is clinically manifested by extrapyramidal, pyramidal, and cerebellar dysfunction. A patient with the type II form of the disease reported improvement in gait and lessened spasticity while taking sulfamethoxazole and trimethoprim (Bactrim) for a noninfectious dysuria syndrome. A double-blind, placebo-controlled trial of Bactrim utilizing a subjective performance scale, physical examination, and six timed tests was performed in this patient. Results revealed lessened spasticity, improvement in walker-assisted gait, and correlative subjective responses. These results suggest an antispasticity effect of Bactrim or one of its components in this patient.     

Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation

Parkin disease is usually autosomal recessive; however, two studies have shown that asymptomatic heterozygotes have nigrostriatal dysfunction and even manifest subtle extrapyramidal signs. The authors used 18F-dopa PET to study 13 asymptomatic parkin heterozygotes and found a significant reduction of (18)F-dopa uptake in caudate, putamen, ventral, and dorsal midbrain compared with control subjects. Four had subtle extrapyramidal signs. Parkin heterozygosity is a risk factor for nigrostriatal dysfunction and in some may contribute to late-onset Parkinson disease.     

Olfactory dysfunction in temporal lobe epilepsy: a case of ictus-related parosmia

Olfactory abnormalities in temporal lobe epilepsy (TLE) usually involve either brief hallucinations prior to seizures or chronic impairments in odor discrimination and identification. We describe the case of a man (B.C.) with TLE with an unusual presentation, an ictus-related parosmia. B.C. reported distorted perception of odor quality and hedonics that could provoke nausea and gagging, typically at its most extreme in the week or so following a seizure. Measures of B.C.'s olfactory functioning were obtained at stages of the ictal cycle when parosmia symptoms were severe and when they had decreased. Unlike other parosmics, B.C.'s detection thresholds were always normal, and unlike others with TLE, he evidenced little impairment in identification or discrimination. Testing during a period of more severe parosmia suggested that B.C.'s experiences might be the result of hedonic changes. We argue this may be the effect of seizure activity on the amygdala, which is known to be involved in mediating emotive reactions to odors.     

Autonomic nervous system dysfunction in Parkinson''s disease: relationships with age, medication, duration, and severity.

Heart rate variability at rest, during deep breathing, or standing up and with the Valsalva manoeuvre did not differ significantly between 67 patients with idiopathic Parkinson's disease (PD) and 31 healthy age matched controls. Blood pressure (BP) responses to standing up and sustained handgrip revealed diminished autonomic function in the PD group. In a preliminary analysis of the PD group older age, anti-Parkinson medication and higher Hoehn and Yahr (HY) stages were each associated with poor autonomic responsiveness. Disease duration was only related to the systolic BP fall on standing up. Multiple stepwise regression analysis showed that older age explained most of the variance of heart rate variability (up to 36%), and the only significant PD related factor was the use of medication, which explained less than 7%. The HY stage accounted for 12.7% of the variance in the standing up BP test, and the use of medication explained 10.6% of the variance of the systolic BP change in the sustained hand grip test. The unmedicated PD subgroup (n = 33), who had mild disease of short duration, showed no evidence of autonomic dysfunction. Cardiovascular autonomic dysfunction in PD is mild, mainly affects blood pressure responses, and occurs only in advanced cases.     

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension

OBJECTIVES: To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS: Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS: Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS: Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.     

MRI-visible perivascular space volumes,sleep duration and daytime dysfunction in adults with cerebrovascular disease

ObjectivesRecent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.MethodsWe analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.ResultsIndividuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38–22.26, p = 0.018).ConclusionsIndividuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.     

Startle reflex hyporeactivity in Parkinson's disease: An emotion-specific or arousal-modulated deficit?

We previously reported that patients with Parkinson's disease (PD) demonstrate reduced psychophysiologic reactivity to unpleasant pictures as indexed by diminished startle eyeblink magnitude [Bowers, D., Miller, K., Bosch, W., Gokcay, D., Pedraza, O., Springer, U., et al. (2006). Faces of emotion in Parkinsons disease: Micro-expressivity and bradykinesia during voluntary facial expressions. Journal of the International Neuropsychological Society, 12(6), 765–773; Bowers, D., Miller, K., Mikos, A., Kirsch-Darrow, L., Springer, U., Fernandez, H., et al. (2006). Startling facts about emotion in Parkinson's disease: Blunted reactivity to aversive stimuli. Brain, 129(Pt 12), 3356–3365]. In the present study, we tested the hypothesis that this hyporeactivity was primarily driven by diminished reactivity to fear-eliciting stimuli as opposed to other types of aversive pictures. This hypothesis was based on previous evidence suggesting amygdalar abnormalities in PD patients, coupled with the known role of the amygdala in fear processing. To test this hypothesis, 24 patients with Parkinson's disease and 24 controls viewed standardized sets of emotional pictures that depicted fear, disgust (mutilations, contaminations), pleasant, and neutral contents. Startle eyeblinks were elicited while subjects viewed these emotional pictures. Results did not support the hypothesis of a specific emotional reactivity deficit to fear pictures. Instead, the PD patients showed reduced reactivity to mutilation pictures relative to other types of negative pictures in the context of normal subjective ratings. Further analyses revealed that controls displayed a pattern of increased startle eyeblink magnitude for “high arousal” versus “low arousal” negative pictures, regardless of picture category, whereas startle eyeblink magnitude in the PD group did not vary by arousal level. These results suggest that previous findings of decreased aversion-modulated startle is driven by reduced reactivity to highly arousing negative stimuli rather than to a specific category (i.e., fear or disgust) of emotion stimuli.     

Tardive parkinsonism in a bipolar patient: Post-mortem examination supports a physiological rather than pathological dysfunction

We describe a case of tardive parkinsonism in the setting of bipolar syndrome, and we offer pathological confirmation that idiopathic Parkinson disease was not the underlying etiology. A 74-year-old Hispanic woman with a history of bipolar disease was noted to have oro-buccal-lingual chorea and parkinsonian symptoms such as resting tremor, rigidity, bradykinesia, and gait disorder persisting several months after neuroleptic discontinuation. She had minor improvement in ambulation with levodopa treatment, and she significantly improved in ambulation only during her manic states. Examination of the subject's post-mortem brain revealed no explicit evidence of degeneration in substantia nigra or other brainstem centers, and no nigral or cortical Lewy bodies were present. Glial cytoplasmic inclusions (characteristic of multiple systems atrophy) and globose neurofibrillary tangles (seen in progressive supranuclear palsy) were not seen either. This patient's presentation was most consistent with neuroleptic-induced parkinsonism and tardive dyskinesia; the etiology was likely related to previous neuroleptic exposure.