Subthalamic stimulation for Parkinson's disease--living better electrically?
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Animals↗
Biomedical subjects
Anthony E Lang
Publications and source records attributed to Anthony E Lang.
The cerebellothalamocortical pathway in essential tremor.
The cerebellum is implicated in the pathogenesis of essential tremor (ET). The authors examined the excitability of the cerebellothalamocortical pathway in ET and found it to be normal. Tremor reset occurred with motor cortex stimulation but not with cerebellar stimulation. These findings suggest that the abnormal oscillatory activity in ET does not originate in the cerebellar cortex but are consistent with the abnormal activity being transmitted through the cerebellothalamocortical pathway being driven by abnormal cerebellar afferent input from areas such as the inferior olive.
Adult↗
Short and long latency afferent inhibition in Parkinson's disease.
Sensory abnormalities have been reported in Parkinson's disease and may contribute to the motor deficits. Peripheral sensory stimulation inhibits the motor cortex, and the effects depend on the interstimulus interval (ISI) between the sensory stimulus and transcranial magnetic stimulation (TMS) to the motor cortex. Short latency afferent inhibition (SAI) occurs at an ISI of approximately 20 ms, and long latency afferent inhibition (LAI) at an ISI of approximately 200 ms. We studied SAI and LAI in 10 Parkinson's disease patients with the aim of assessing whether sensorimotor processing is altered in Parkinson's disease. Patients were studied on and off medication, and the findings were compared with 10 age-matched controls. Median nerve and middle finger stimulation were delivered 20-600 ms before TMS to the contralateral motor cortex. The motor evoked potentials were recorded from the relaxed first dorsal interosseous (FDI) muscle. SAI was normal in Parkinson's disease patients off dopaminergic medications, but it was reduced on the more affected side in Parkinson's disease patients on medication. LAI was reduced in Parkinson's disease patients compared with controls independent of their medication status. LAI reduced long interval intracortical inhibition in normal subjects but not in Parkinson's disease patients. The different results for SAI and LAI indicate that it is likely that separate mechanisms mediate these two forms of afferent inhibition. SAI probably represents the direct interaction of a sensory signal with the motor cortex. This pathway is unaffected by Parkinson's disease but is altered by dopaminergic medication in Parkinson's disease patients and may contribute to the side effects of dopaminergic drugs. LAI probably involves other pathways such as the basal ganglia or cortical association areas. This defective sensorimotor integration may be a non-dopaminergic manifestation of Parkinson's disease.
Adult↗
Progression of gait, speech and swallowing deficits in progressive supranuclear palsy.
OBJECTIVE: To identify outcome measures for clinical trials in progressive supranuclear palsy (PSP), the authors determined the time to key motor impairments in a well-defined patient cohort. METHODS: The records of consecutive patients with probable PSP, defined by National Institute of Neurological Disorders and Stroke-Society for Progressive Supranuclear Palsy workshop criteria on first visit to a tertiary care center, were selected for study if the patients were seen regularly at 3- to 6-month intervals, had at least 24 months of care at the Rush movement disorder center, and were originally seen in the movement disorder center before any of the following key motor impairments developed: unintelligible speech, no independent walking, inability to stand unassisted, wheelchair-bound, or recommendation for feeding tube placement. Using standardized criteria from the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr stages taken at each clinic visit, the authors recorded the time that each patient reached the key motor impairments and death. Median months from first symptom onset and from first consultation at the movement disorder center to each motor impairment were derived from Kaplan-Meier curves. RESULTS: Fifty subjects, mean age at study entry 64.2 years, were followed to death (n = 21, mean duration of surveillance 53.6 months) or in ongoing fashion (n = 29, mean duration of surveillance 46.2 months). Eighty-eight percent of the sample met at least one milestone. The median time from disease onset to the first key motor impairment was 48 months, 24 months after first consultation. The three gait items occurred temporally close, and the authors considered them thereafter as a single milestone, occurring at a median disease duration of 57 months, 34 months after first consultation. Unintelligible speech occurred at a median disease duration of 71 months, median 44 months after first consultation. As a composite end point, speech/gait accounted for 98% of the sample's first key motor impairment. Need for nasogastric tube was rarely the first milestone (8%). CONCLUSIONS: Gait impairment and unintelligible speech are milestones that occur rapidly in PSP and can be monitored with standardized rating scales. The authors suggest that clinical trials use these indices to assess how interventions alter anticipated progression of clinical deterioration in PSP.
Adult↗
The fragile X premutation presenting as essential tremor.
CONTEXT: The fragile X premutation has recently been reported to be associated with a neurodegenerative syndrome, chiefly characterized by intention tremor, gait ataxia, and executive cognitive deficits in men older than 50 years. Essential tremor is a frequent cause of tremor in elderly patients and in some cases is associated with impaired tandem gait and cognitive deficits. OBJECTIVE: To describe 2 fragile X carriers whose clinical presentation mimicked essential tremor. DESIGN: The 2 patients described herein underwent neurologic examinations by experienced movement disorders neurologists, magnetic resonance imaging, and fragile X gene, messenger RNA, and protein analyses. One underwent detailed neuropsychological testing. SETTING: Patients were studied at 2 large university movement disorders clinics. PATIENTS: Both patients were white men older than 50 years who had been diagnosed as having essential tremor and then found to be fragile X carriers. RESULTS: Besides disabling intention tremor, the 2 patients had impaired tandem, generalized brain atrophy, and unusual bilateral T2 middle cerebellar hyperintensities on magnetic resonance imaging. The patient who underwent neuropsychological testing had frontal executive deficits. Both patients had elevated fragile X mental retardation gene 1 messenger RNA and reduced fragile X mental retardation 1 protein levels. CONCLUSION: The fragile X carrier state may underlie the clinical findings in some older men diagnosed as having essential tremor.
Aged↗
Motor cortical stimulation for parkinsonism in multiple system atrophy.
BACKGROUND: Functional neuroimaging studies have demonstrated disturbances in the activity of premotor and motor cortices in Parkinson disease and in animal models of parkinsonism that improve in response to effective basal ganglia surgical therapy. Techniques that directly alter the function of these cortical areas, such as transcranial magnetic stimulation, have been applied in patients with Parkinson disease, with transient improvement in their bradykinesia and gait dysfunction. Recently, a patient with refractory Parkinson disease was claimed to have obtained a marked bilateral clinical benefit from extradural unilateral motor cortical stimulation. We hypothesized that direct cortical stimulation could alleviate the disability of the treatment-refractory parkinsonian symptoms commonly present in MSA. OBJECTIVE: To evaluate the efficacy of motor cortical stimulation in patients with refractory parkinsonism due to multiple system atrophy (MSA). METHODS: Five patients with a diagnosis of MSA with predominant parkinsonism underwent surgery for subdural motor cortical stimulation. MAIN OUTCOME MEASURES: Changes in activities of daily living and motor subscores on the Unified Parkinson's Disease Rating Scale 12 hours after medication withdrawal. Scores at baseline and 3 to 6 months following surgery were compared. RESULTS: All patients had a decline in motor scores at the follow-up evaluations despite the application of a variety of adjustments. The activities of daily living score mildly worsened by 9.7% (95% confidence interval, 32.3 to-13.0; P =.37) and the motor score worsened by 25.6% (95% confidence interval, 58.7 to -7.5; P =.06). Despite objective worsening over time and no deterioration when stimulation was immediately turned off, 3 patients still claimed subjective benefit and requested continued stimulation. No patients suffered adverse effects from the surgery or long-term stimulation, although 1 patient had a stimulation-induced seizure during the initial programming. The range of settings for 4 patients with bipolar configuration and 1 patient with monopolar configuration were as follows: amplitude, 3 to 3.6 V; pulse width, 40 to 90 milliseconds; and pulse rate, 145 to 185 Hz. CONCLUSIONS: Our data suggest that motor cortical stimulation using these parameters fails to improve the motor disability in MSA. Worsening of motor scores was likely a function of disease progression.
Activities of Daily Living↗
Pallidal neuronal activity: implications for models of dystonia.
Dystonia is a neurological syndrome involving sustained contractions of opposing muscles leading to abnormal movements and postures. Recent studies report abnormally low pallidal neuronal activity in patients with generalized dystonia, suggesting hyperkinetic disorders result from underactive basal ganglia output. We examined this hypothesis in 11 patients with segmental and generalized dystonia undergoing microelectrode exploration of the internal globus pallidus (GPi) before pallidotomy or deep brain stimulation (DBS) implantation. The mean firing rates and firing patterns were compared with those in six patients with Parkinson's disease (PD). In seven patients who underwent surgery under local anesthesia, the mean GPi firing rate was 77 Hz, similar to the 74 Hz observed in the PD patients. However, in three dystonic patients under propofol anesthesia, GPi mean firing rate was much reduced (31 Hz), and the firing pattern was distinguished by long pauses in activity, as reported by others. Low-dose propofol in one other dystonia patient also seemed to suppress GPi firing. These results indicate that an abnormally low basal ganglia output is not the sine qua non of dystonia. The widely accepted pathophysiological models of dystonia that propose global decreases in basal ganglia output need to be viewed with caution in light of these findings.
Adolescent↗
Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia.
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Basal Ganglia↗
Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study.
Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using (18)F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2-year, randomized, double-blind, multinational study compared the rates of loss of dopamine-terminal function in de novo patients with clinical and (18)F-dopa PET evidence of early PD, randomized 1 to 1 to receive either ropinirole or levodopa. The primary outcome measure was reduction in putamen (18)F-dopa uptake (Ki) between baseline and 2-year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with ropinirole (-13.4%; n = 68) compared with levodopa (-20.3%; n = 59; 95% confidence interval [CI], 0.65-13.06). Statistical parametric mapping localized lesser reductions in (18)F-dopa uptake in the putamen and substantia nigra with ropinirole. The greatest Ki decrease in each group was in the putamen (ropinirole, -14.1%; levodopa, -22.9%; 95% CI, 4.24-13.3), but the decrease was significantly lower with ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by (18)F-dopa PET.
Adult↗
Benign hereditary chorea: clinical, genetic, and pathological findings.
Benign hereditary chorea is an autosomal dominant disorder presenting with childhood-onset chorea, no dementia, and little or no progression. We present a family with typical clinical features of benign hereditary chorea. Pathological investigation of the brain of an affected family member who died of an unrelated condition showed no significant gross or histological abnormalities. Genetic evaluation showed a novel single nucleotide substitution of intron 2 of the TITF-1 gene (also referred to as TTF, NKX2.1, and T/ebp) on chromosome 14 which is predicted to have drastic consequences on the maturation processes of TITF-1.
Amino Acid Substitution↗
Early-onset Parkinson's disease caused by a compound heterozygous DJ-1 mutation.
Mutations in DJ-1 have been linked to an autosomal recessive form of early-onset parkinsonism. To identify mutations causing Parkinson's disease (PD), we sequenced exons 1 through 7 of DJ-1 in 107 early-onset (age at diagnosis up to 50 years) PD subjects. One subject had a frameshift mutation in the first coding exon and an exon 7 splice mutation both predicted to result in a loss of functional protein. This subject was diagnosed with probable PD at age 24 years with asymmetric onset and an excellent response to levodopa therapy. Our observations suggest that sequence alterations in DJ-1 are a rare cause of early-onset PD.
Adult↗
Frequency of parkin mutations in late-onset Parkinson's disease.
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Adult↗
Acute effect of transcutaneous electrical nerve stimulation on tremor.
Based on the claims that transcutaneous electrical nerve stimulation is effective in myoclonic dystonia and essential tremor, we evaluated its acute effects in 5 patients with essential tremor and 2 patients with tremor attributed to peripheral neuropathy using as parameters the Washington Heights-Inwood Genetic Study of Essential Tremor rating scale, self-reported impression, and recording of electromyographic activity. We found no significant improvement in any of the parameters tested.
Aged↗
Neurodegenerative disease and the evolution of art: the effects of presumed corticobasal degeneration in a professional artist.
Production of art is a complex process involving a combination of technical skill and a unique talent. Changes in artistic ability may accompany neurodegenerative disorders when they occur in an artist. The nature of these changes in the context of definable regional neuropathological disturbances may provide insight into the structural basis of the creative process. We describe a professional artist in whom presumed corticobasal degeneration (CBD) was associated with an alteration of his artistic judgement and production. Disinhibition, perseveration, and left hemispatial neglect, features of his cognitive profile were readily discernible in his work. The differences in his style are examined with respect to his main neuroanatomic abnormalities, namely right cerebral hemiatrophy as defined by magnetic resonance and single-photon emission computed tomography imaging. Cognitive deficits, including visuoconstructive and motor neglect, apathy, perseveration, and disinhibition as determined by neuropsychological testing, contributed to the dissolution of his artistic skills. Our case study adds to the growing literature on the effects of brain damage on artistic expression in the graphic arts.
Aged↗
Corticobasal degeneration syndrome with basal ganglia calcification: Fahr's disease as a corticobasal look-alike?
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Basal Ganglia Diseases↗
Unique form of propriospinal myoclonus as a possible complication of an enteropathogenic toxin.
Propriospinal myoclonus is an uncommon form of spinal myoclonus propagated, presumably, by slowly conducting polysynaptic intraspinal pathways. Although most patients demonstrate no clear etiology, a variety of disorders have been linked to this abnormal movement, including trauma, multiple sclerosis, tumors, and infectious disorders such as herpes zoster, human immunodeficiency virus, and Lyme disease. We describe 2 young male patients from the same town in Northern Ontario, Canada, exposed to an outbreak of Escherichia coli O157:H7 from contaminated municipal water, who developed identical clinical and electrophysiological features suggestive of a rhythmic form of propriospinal myoclonus with activity alternating between abdominal and paraspinal muscles. A toxin-mediated microvascular thrombosis is proposed as a possible pathogenic mechanism underlying this novel association.
Adult↗
Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders.
As there are no biological markers for the antemortem diagnosis of degenerative parkinsonian disorders, diagnosis currently relies upon the presence and progression of clinical features and confirmation depends on neuropathology. Clinicopathologic studies have shown significant false-positive and false-negative rates for diagnosing these disorders, and misdiagnosis is especially common during the early stages of these diseases. It is important to establish a set of widely accepted diagnostic criteria for these disorders that may be applied and reproduced in a blinded fashion. This review summarizes the findings of the SIC Task Force for the study of diagnostic criteria for parkinsonian disorders in the areas of Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. In each of these areas, diagnosis continues to rest on clinical findings and the judicious use of ancillary studies.
Biomarkers↗
Corticobasal degeneration: selected developments.
Corticobasal degeneration (CBD) is now classified as a four-repeat tauopathy. The presence of neuronal and glial tau-immunoreactive lesions is critical to the pathological diagnosis. It is increasingly recognised that a variety of clinical phenotypes can occur as a consequence of this pathological state and that several other pathological conditions may be associated with the perceptuo-motor syndrome first associated with the pathological features of CBD (now referred to as the corticobasal syndrome). The high rate of diagnostic inaccuracy must be considered when interpreting previous literature dealing with cases presumed to be CBD. There is considerable clinical, pathological, and genetic overlap between CBD and progressive supranuclear palsy (PSP); however, the etiological and pathogenetic relationships between the two remain uncertain. There are reasons to believe that these diseases could be different phenotypes of a single process. Even if they are eventually found to be distinct disorders, treatments that alter the progression of one may have similar ameliorative effects on the other. Each of these issues are discussed in this selective review of CBD.
Diagnosis, Differential↗