Biomedical subjects
Stephen G Reich
Publications and source records attributed to Stephen G Reich.
Delineation of the motor disorder of Lesch-Nyhan disease.
Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.
Adult-onset primary lower limb dystonia.
The lower extremity is affected infrequently in adult-onset primary dystonia in contrast to childhood-onset dystonia, which typically begins in the foot. When dystonia affects the foot in an adult, it is usually on a secondary basis. We present findings on 17 patients (11 women, 6 men; average age of onset 48.4 years; average time to diagnosis 2.7 years) with adult-onset primary foot dystonia. Prior to diagnosis, most patients underwent extensive testing and treatment, including unnecessary surgeries. Only the left lower extremity was involved in 8 patients, only the right in 7, and both in 2. The most common patterns were plantar flexion of all toes and inversion of the foot, typically activated with standing or walking. Only 2 patients had dystonia elsewhere. There was a family history of possible dystonia in 2 patients. One of five tested for DYT1 was positive, in the absence of a family history. One of eight patients treated with levodopa experienced mild improvement. Six of eight treated with botulinum toxin improved. No patient has been observed to have a secondary cause of dystonia. The prognosis, with regard to progression or spread to other body parts, has been favorable. Although uncommon, foot dystonia on a primary basis, not due to DYT1, can begin in adulthood. In this series of patients, the diagnosis was often not recognized, leading to extensive and unnecessary testing and treatment and emphasizing the need for wider recognition.
Subjective report versus objective measurement of activities of daily living in Parkinson's disease.
We compared subjective self-reports with objective performance ratings of activities of daily living (ADLs) and instrumental ADLs (IADLs) in patients with Parkinson's disease (PD) and identified variables associated with discordance of ratings between these two methods. Seventy-six PD patients completed a modified Older Americans Resources and Services scale, assessing ADLs and IADLs. These results were compared with structured performance tests of walking, eating, dressing, money, and medicine management administered in the clinic. Patient performance was rated on a five-point Likert-type scale, ranging from 1 = no difficulty to 5 = completely unable to perform task. Significant differences were found between patients and clinicians' ratings on all tasks except walking. On the other four tasks, paired group t tests showed that patients reported better function compared with the clinician rating of medication management (1.33 vs. 2.80), eating (1.53 vs. 1.76), dressing (1.64 vs. 1.86), and managing money (1.44 vs. 2.06). A discrepancy was found between patients subjective reporting of ADL and IADL function and objective ratings. Patients overestimated their function on four of five tasks. Further study is necessary to identify whether subjective or objective performance ratings are more reflective of actual daily function.
Can mid-sagittal MRI be used to diagnose progressive supranuclear palsy?
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Psychogenic movement disorders.
All varieties of movement disorders may be mimicked by a psychogenic disorder, most commonly tremor, dystonia, and myoclonus. Approximately 3% of patients seen in specialty clinics have a psychogenic movement disorder (PMD). The diagnosis of a PMD depends on not just ruling out an organic movement disorder, but moreover, recognizing features from the history and examination that are inconsistent or incongruous with an organic movement disorder. Most PMDs represent a conversion disorder, sometimes as part of a somatoform disorder; less common diagnoses include a factitious disorder or malingering. Co-morbid psychiatric illness is prevalent in patients with PMD including depression, anxiety, and personality disorders. Many PMDs remain chronic, but a multidisciplinary approach centering on psychiatric intervention can be successful. A shorter duration of symptoms and a co-existent treatable psychiatric disorder portend a better prognosis, whereas compensation and pending litigation are associated with a poorer prognosis.
Gustatory sweating: Frey syndrome.
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Progression of dystonia in complex regional pain syndrome.
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West Nile virus presenting as opsoclonus-myoclonus cerebellar ataxia.
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Wilson's disease presenting with an unusual cough.
A 26-year-old man developed an unusual repetitive, nonproductive cough. Extensive pulmonary and otolaryngology investigations failed to disclose a cause. It was only after he developed additional neurological manifestations ultimately leading to the diagnosis of Wilson's disease (WD) that a neurological basis for the cough was suspected. Features of the cough suggest it was a form of respiratory dyskinesia, a previously unreported presentation of WD.
Tardive Dystonia.
Tardive dyskinesia is a movement disorder that develops after exposure to dopamine receptor blocking agents. Less well-appreciated are other, more recently described tardive syndromes that are phenomenologically distinct from tardive dyskinesia and respond to different treatments. Patients may simultaneously have more than one tardive syndrome. Major subtypes of tardive syndromes include tardive dyskinesia, characterized by orobuccolingual, truncal, or appendicular, choreiform movements; tardive dystonia, characterized by sustained, stereotyped muscle spasms of a twisting or turning character; and tardive akathisia, characterized by an inner sense of restlessness or unease. The sensation often is unpleasant and may be accompanied by repetitive, purposeless movements (stereotypies), such as pacing. Less common tardive syndromes include tardive myoclonus, tardive tourettism, and tardive tremor. Tardive syndromes often are a source of great distress and disability to patients and may be permanent, despite discontinuing the responsible medication. Prevention, early detection, and prompt management are the major clinical focus. When a patient develops a tardive syndrome appropriate actions include 1) review of the primary diagnosis that prompted starting a dopamine receptor blocking agent; 2) characterization of the movement disorder(s); 3) where possible, discontinuation of dopamine blocking agent or replacement with a less potent alternative agent; 4) gradual withdrawl of the offending drug because some patients have an exacerbation of a tardive syndrome after abrupt withdrawal; and 5) assessment of the severity of symptoms and development of a treatment plan based on the phenomenology, with the goal of maximizing patient comfort and function. Although tardive dyskinesia typically develops after chronic exposure to dopamine receptor blocking agents, it, and other variants (such as tardive dystonia) can develop very rapidly after treatment. There seems to be no minimal safe duration of exposure for the development of a tardive syndrome. It is important to recognize that anti-emetics, which are dopamine receptor blockers, such as prochlorperazine, promethazine and metoclopramide, can cause tardive syndromes. Clinicians should become familiar with antipsychotic agents that have a lower risk of causing tardive syndromes, such as clozapine, quetiapine, and olanzapine. We review treatment options for tardive dystonia.
Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson's disease.
OBJECTIVE: To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD). METHODS: Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5-10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects. RESULTS: Patients on donepezil showed selective and significant (p<0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases. CONCLUSION: Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases.
The cold hands sign in MSA. Multiple system atrophy.
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Ten most commonly asked questions about the psychiatric aspects of Parkinson's disease.
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Distinguishing progressive supranuclear palsy from other forms of Parkinson's disease: evaluation of new signs.
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