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G K Wenning

Publications and source records attributed to G K Wenning.

At least 19 recordsLinked to original sources
PubMed1998

Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study.

BACKGROUND: Whether Parkinson disease (PD) and dementia with Lewy bodies (DLB) represent 2 distinct nosologic entities or are diverse phenotypes of Lewy body disease is subject to debate. OBJECTIVES: To determine the accuracy of the diagnoses of Lewy body disease, PD, and DLB by validating the clinical diagnoses of 6 neurologists with the neuropathologic findings and to identify early predictors of the diagnoses. METHODS: Six raters who were unaware of the neuropathologic diagnoses analyzed 105 clinical vignettes corresponding to 29 cases of Lewy body disease (post hoc analysis of 15 patients with PD and 14 with DLB) and 76 patients without PD or DLB whose cases were confirmed through autopsy findings. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value (PPV) were chosen as validity measures and the K statistic as a reliability measure. RESULTS: Interrater reliability for the diagnoses of Lewy body disease and PD was moderate for the first visit and substantial for the last, whereas agreement for diagnosis of DLB was fair for the first visit and slight for the last. Median sensitivity for diagnosis of Lewy body disease was 56.9% for the first visit and 67.2% for the last; median PPV was 60.0% and 77.4%, respectively. Median sensitivity for the diagnosis of PD was 73.3% for the first visit and 80.0% for the last; median PPV was 45.9% and 64.1%, respectively. Median sensitivity for the diagnosis of DLB was 17.8% for the first visit and 28.6% for the last; median PPV was 75.0% for the first visit and 55.8% for the last. The raters' results were similar to those of the primary neurologists. Several features differentiated PD from DLB, predicted each disorder, and could be used as clinical pointers. CONCLUSIONS: The low PPV with relatively high sensitivity for the diagnosis of PD suggests overdiagnosis. Conversely, the extremely low sensitivity for the diagnosis of DLB suggests underdiagnosis. Although the case mix included in the study may not reflect the frequency of these disorders in practice, limiting the clinical applicability of the validity measures, the raters' results were similar to those of the primary neurologists who were not exposed to such limitations. Overall, our study confirms features suggested to predict these disorders, except for the early presence of postural imbalance, which is not indicative of either disorder.

Adult↗
PubMed1998

The natural history of Parkinson's disease.

There are still insufficient data on the natural course of Parkinson's disease (PD) owing to lack of standardized longitudinal follow-up studies. Reported progression rates in early PD vary considerably by a factor of 2 to 3. Similarly, data from sequential [18F]dopa PET studies in PD patients have produced variable decline rates of PET indices ranging between 7 and 70% per decade. Risk factors for rapid progression include old age at onset, concomitant major depression, dementia, and akinetic-rigid symptom presentation. The introduction of levodopa into the routine treatment of PD patients had a dramatic impact on symptomatic control without affecting the underlying rate of disease progression. By contrast, monoamine oxidase (MAO) B inhibition by deprenyl monotherapy in early PD was shown to delay the need for levodopa by around 9 months. However, the neuroprotective action disappeared after 2 years of follow-up. Furthermore, deprenyl also failed to influence the subsequent development of levodopa-induced motor complications. Available studies on mortality in PD provide heterogeneous mortality rates, probably because of discrepancies between patient populations with respect to co-morbidity, disease stage at study entry, and diagnostic accuracy. However, the most recent follow-up from the DATATOP cohort suggests normal life expectancy in carefully selected patients without significant co-morbidity and with adequate treatment and expert follow-up.

Cell Count↗
PubMed1998

123I-beta-CIT and 123I-IBZM-SPECT scanning in levodopa-naive Parkinson's disease.

Striatal dopamine transporter function and dopamine D2 receptor status were evaluated in 15 patients with early untreated Parkinson's disease using single photon emission tomography (SPECT) with 123I-Iodo-2beta-carboxymethoxy-3beta-(4-idiophenyl)tropane (beta-CIT) and 123I-Iodobenzamide (IBZM) as pre- and postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but asymmetric in 10 patients. Patients with bilateral symptoms had significantly lower 18-hour striatal/cerebellar beta-CIT binding ratios (3.59 +/- 0.79) than hemiparkinsonian patients (5.76 +/- 1.48, p < 0.05) reflecting more advanced disease in this subgroup. Patients with bilateral parkinsonism were also found to have a significant side-to-side difference in striatal beta-CIT binding with more marked reduction contralateral to the presenting limb (18-hour striatal/cerebellar ratio: 4.13 +/- 0.78 [ipsilateral] versus 3.59 +/- 0.79 [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was significantly elevated contralateral to the affected side in hemiparkinsonian patients (striatal/cerebellar ratio: 2.42 +/- 0.90 [contralateral] versus 2.19 +/- 0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 +/- 0.43 [contralateral to more severely affected side] versus 1.83 +/- 0.34 [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor upregulation contralateral to the presenting side occurs in untreated unilateral PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss of dopamine transporter function. Combined beta-CIT and IBZM SPECT studies may be helpful to monitor the progression of nigrostriatal dysfunction in early PD.

Aged↗
PubMed1998

Retrospective application of a set of clinical diagnostic criteria for the diagnosis of multiple system atrophy.

We estimated the accuracy of a modified commonly used set of clinical diagnostic criteria for the diagnosis of multiple system atrophy (MSA) by retrospectively applying the criteria to the features recorded by six neurologists who had evaluated 105 autopsy-confirmed cases (16 MSA and 89 non-MSA disorders). Cases were abstracted from the records of the patients' first visit to an academic center, and were presented as clinical vignettes to six neurologists, each of whom recorded the main clinical features of the presented clinical vignette on a standardized form. Sensitivity and positive predictive values were chosen as validity outcome measures and were calculated by comparing the applied diagnostic criteria to the neuropathologic information. Of note, most MSA patients in this study (mainly those with Shy-Drager type) had not received levodopa therapy since the primary neurologists often had not perceived a need to administer this treatment. The validity of the retrospectively applied criteria for the diagnosis of possible MSA (sensitivity: median, 53%, range, 50-69%; positive predictive value: 30%, 28-39%) and probable MSA (sensitivity: 44%, 31-60%; positive predictive value: 68%, 54-80%) at the first visit was suboptimal. The best, still not perfect, accuracy for this set of diagnostic criteria was obtained when six out of eight features (sporadic adult onset, dysautonomia, parkinsonism, pyramidal signs, cerebellar signs, no levodopa response, no cognitive dysfunction, or no downward gaze supranuclear palsy) were present (median sensitivity, 59%; range, 50-75%; positive predictive value: 67%, 53-83%). This is the first study to validate criteria for the clinical diagnosis of MSA. Our data suggest that it is difficult to achieve an early and accurate clinical diagnosis of this disorder. The probability of correctly diagnosing MSA increases when at least six features of this modified set of criteria are present or when requiring the set for probable MSA.

Adult↗
PubMed1998

Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination.

OBJECTIVE: To analyse the natural history and survival of corticobasal degeneration by investigating the clinical features of 14 cases confirmed by postmortem examination. METHODS: Patients with definite corticobasal degeneration were selected from the research and clinical files of seven tertiary medical centres in Austria, the United Kingdom, and the United States. Clinical features were analysed in detail. RESULTS: The sample consisted of eight female and six male patients; mean age at symptom onset was 63 (SD 7.7) years, and mean disease duration was 7.9 (SD 2.6) years. The most commonly reported symptom at onset included asymmetric limb clumsiness with or without rigidity (50%) or tremor (21%). At the first neurological visit, on average 3.0 (SD 1.9) years after symptom onset, the most often encountered extrapyramidal features included unilateral limb rigidity (79%) or bradykinesia (71%), postural imbalance (45%), and unilateral limb dystonia (43%). Ideomotor apraxia (64%), and to a lesser extent cortical dementia (36%), were the most common cortical signs present at the first visit. During the course of the disease, virtually all patients developed asymmetric or unilateral akinetic rigid parkinsonism and a gait disorder. No patient had a dramatic response to levodopa therapy. Median survival time after onset of symptoms was 7.9 (SD 0.7) (range, 2.5-12.5) years, and, after the first clinic visit, 4.9 (SD 0.7) (range, 0.8-10) years. Early bilateral bradykinesia, frontal syndrome, or two out of tremor, rigidity, and bradykinesia, predicted a shorter survival. CONCLUSION: The results confirm that unilateral parkinsonism unresponsive to levodopa and limb ideomotor apraxia are the clinical hallmarks of corticobasal degeneration, and only a minority of patients with corticobasal degeneration present with dementia. The study also suggests that a focal cognitive and extrapyramidal motor syndrome is indicative of corticobasal degeneration. Survival in corticobasal degeneration was shortened by the early presence of (more) widespread parkinsonian features or frontal lobe syndrome.

Aged↗
PubMed1997

What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study.

BACKGROUND: The presentation of symptoms for multiple system atrophy (MSA) varies. Because there are no specific markers for its clinical diagnosis, the diagnosis rests on the results of the neuropathologic examination. Despite several clinicopathologic studies, the diagnostic accuracy for MSA is unknown. OBJECTIVES: To determine the accuracy for the clinical diagnosis of MSA and to identify, as early as possible, those features that would best predict MSA. DESIGN: One hundred five autopsy-confirmed cases of MSA and related disorders (MSA [n=16], non-MSA [n=89]) were presented as clinical vignettes to 6 neurologists (raters) who were unaware of the study design. Raters identified the main clinical features and provided a diagnosis based on descriptions of the patients' first and last clinic visits. METHODS: Interrater reliability was evaluated with the use of kappa statistics. Raters' diagnoses and those of the primary neurologists (who followed up the patients) were compared with the autopsy-confirmed diagnoses to estimate the sensitivity and positive predictive values at the patients' first and last visits. Logistic regression analysis was used to determine the best predictors to diagnose MSA. RESULTS: For the first visit (median, 42 months after the onset of symptoms), the raters' sensitivity (median, 56%; range, 50%-69%) and positive predictive values (median, 76%; range, 61%-91%) for the clinical diagnosis of MSA were not optimal. For the last visit (74 months after the onset of symptoms), the raters' sensitivity (median, 69%; range, 56%-94%) and positive predictive values (median, 80%; range, 77%-92%) improved. Primary neurologists correctly identified 25% and 50% of the patients with MSA at the first and last visits, respectively. False-negative and -positive misdiagnoses frequently occurred in patients with Parkinson disease and progressive supranuclear palsy. Early severe autonomic failure, absence of cognitive impairment, early cerebellar symptoms, and early gait disturbances were identified as the best predictive features to diagnose MSA. CONCLUSIONS: The low sensitivity for the clinical diagnosis of MSA, particularly among neurologists who followed up these patients in the tertiary centers, suggests that this disorder is underdiagnosed. The misdiagnosis of MSA is usually due to its confusion with Parkinson disease or progressive supranuclear palsy, thus compromising the research on all 3 disorders.

Aged↗
PubMed1997

Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease.

Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.

Adult↗
PubMed1997

Cerebellar presentation of multiple system atrophy.

Early diagnosis of multiple-system atrophy (MSA) is important in patients presenting with late-onset cerebellar ataxia because it has a less favourable prognosis than other degenerative ataxic disorders. We report cerebellar presentation of MSA in a series of 16 patients, 3 of whom later developed parkinsonism. Two-thirds of them had early evidence of impaired postural reflexes with a history of recurrent falls. Some of these had a narrow-based, unsteady gait, unlike the more classic broad-based gait ataxia of cerebellar disease. On review of the patients' histories, genitourinary dysfunction (particularly impotence) was present at the onset of, or preceding, cerebellar ataxia in 60% of patients, but this had often been attributed to age, or to urological or gynaecological causes. External striated anal or urethral sphincter electromyography (EMG) demonstrated features of chronic denervation and reinnervation in 14 (93%) of 15 patients, consistent with degeneration in Onuf's nucleus as occurs in MSA. Autonomic function tests were abnormal in 9 (64%) of 14 patients. Our data suggest that close enquiry into genitourinary function and analysis of the gait disorder can be useful pointers to a diagnosis of MSA in patients with an unexplained adult-onset progressive cerebellar syndrome, and that sphincter EMG is the most useful investigation in this context.

Adult↗
PubMed1997

Multiple system atrophy: a review of 203 pathologically proven cases.

We report the clinicopathological features of 203 cases of pathologically proven multiple system atrophy (MSA) from 108 publications up to February 1995. The majority of patients showed symptoms in their early fifties, and men were more commonly affected than women (ratio of 1.3:1). Most patients suffered from some degree of autonomic failure (74%). Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%). The response to levodopa was poor in most patients, but there was a subgroup with a good response, who also often developed axial levodopa-induced dyskinesias. Other characteristic features included severe dysarthria, stridor, and, in a few patients, contractures and dystonia (antecollis). Mild or moderate intellectual impairment occurred in some cases, but severe dementing illness was most unusual. The main pathological change comprised cell loss and gliosis in the putamen, caudate nucleus, external pallidum, substantia nigra, locus ceruleus, inferior olives, pontine nuclei, cerebellar Purkinje cells, and intermediolateral cell columns of the spinal cord. However, other neuronal populations were also involved to varying degrees, such as the thalamus, vestibular nucleus, dorsal vagal nucleus, corticospinal tracts, and anterior horn cells. Characteristic glial and/or neuronal cytoplasmic inclusions were identified in all cases in which they were sought, irrespective of clinical presentation. Akinesia correlated with the degree of nigral and putaminal cell loss, whereas rigidity was related only to the later. Tremor was unrelated to cell loss at any site. Ataxia correlated with the degree of olivopontocerebellar atrophy. Pyramidal signs were associated with pyramidal tract pallor. Our analysis also confirmed an association of postural hypotension with intermediolateral cell column degeneration.

Aged↗
PubMed1997

Mitochondrial respiratory chain function in multiple system atrophy.

Multiple system atrophy (MSA) is a clinico-pathological entity distinct from idiopathic Parkinson's disease (PD) that is responsible for 5-10% of cases of parkinsonism. Degeneration of nigral neurones is a feature of both diseases. A specific deficiency of mitochondrial complex I activity has been found in PD substantia nigra. We have analysed mitochondrial function in substantia nigra and platelets from MSA patients to identify any respiratory chain defect in this disorder and to determine its tissue specificity. As our MSA patients had been on L-DOPA, we also sought to establish whether this treatment could cause the complex I defect as seen in PD. We found no significant difference in respiratory chain activity corrected for mitochondrial mass between control and MSA patients in either of the tissues studied. These results provide a biochemical dimension to the differences between MSA and idiopathic PD. In addition, the fact that L-DOPA failed to induce a complex I defect in MSA substantia nigra suggests that this treatment is unlikely to cause the complex I deficiency in PD, without additional factors that may operate in PD.

Aged↗
PubMed1997

Supranuclear gaze palsy and eyelid apraxia in postencephalitic parkinsonism.

We describe six patients with clinicopathologically confirmed post-encephalitic parkinsonism (PEP) in whom oculomotor abnormalities developed several years after suffering the initial episode of encephalitis lethargica. Four of the cases had vertical supranuclear gaze palsy and two eyelid apraxia, features typically associated with progressive supranuclear palsy (PSP). Our findings indicate that the presence of gaze palsy alone may not be a reliable clinical discriminator between PEP and PSP. Involvement of the dorsal central gray nucleus, nucleus centralis pontis oralis, nucleus dorsal raphe interpositus, rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), nucleus interstitialis of Cajal, nucleus of the posterior commissure, pedunculopontine nuclei and frontal cortex was observed in several of our PEP cases and may contribute to the oculomotor abnormalities in this disorder. Whether the dorsal tegmental nucleus, caudal to the supratrochlear nucleus, severely affected in all our PEP cases, has a role in vertical gaze needs to be further studied.

Adult↗
PubMed1997

Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.

Aged↗
PubMed1997

[Atypical Parkinson syndrome].

Various clinico-pathological studies have shown that appr. 20% of patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD) may have neuropathological evidence of alternative causes of parkinsonism. Most of these misdiagnosed "IPD" patients meet clinical criteria for either multiple system atrophy (MSA), or progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD). A careful history and physical examination, as well as follow-ups and selected investigations are essential for an accurate clinical diagnosis of these atypical parkinsonian syndromes. The following paper therefore provides a review of clinical features and diagnostic findings in MSA, PSP and CBD, in order to facilitate recognition of these patients.

Brain↗
PubMed1997

Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study.

The accuracy of the clinical diagnosis of corticobasal degeneration (CBD) is unknown. To determine its diagnostic accuracy, we presented 105 cases with known neuropathologic diagnoses, including CBD (n = 10), progressive supranuclear palsy (PSP, n = 24), Parkinson's disease (n = 15), diffuse Lewy body disease (n = 14), multiple system atrophy (n = 16), postencephalitic parkinsonism (n = 7), Pick's disease (n = 7), Creutzfeldt-Jakob disease (n = 4), Alzheimer's disease (n = 4), vascular parkinsonism (n = 3), and Whipple's disease (n = 1), as clinical vignettes to six neurologists unaware of the autopsy findings. Reliability was measured with the kappa statistics. The neurologists' clinical diagnoses were compared with clinicopathologic diagnoses for sensitivity, specificity, and positive predictive values at first and last clinic visits. The group reliability for the diagnosis of CBD significantly improved from moderate for the first visit (mean = 34 months after onset) to substantial for the last (68 months after onset). For the first visit, mean sensitivity for CBD was low (35%), but specificity was near-perfect (99.6%). For the last visit, mean sensitivity minimally increased (48.3%), and specificity remained stable. False-negative misdiagnoses mainly occurred with PSP. False-positive diagnoses were rare. The extremely low sensitivity of the clinical diagnosis of CBD suggests that this disorder is markedly underdiagnosed. Although the validity of the clinical diagnosis might have been improved if neurologists could have examined these patients, more important is that this disorder was misdiagnosed by the primary neurologists. In our data set, the best predictors for the diagnosis of CBD included limb dystonia, ideomotor apraxia, myoclonus, and asymmetric akinetic-rigid syndrome with late onset of gait or balance disturbances.

Basal Ganglia↗
PubMed1997

Survival of patients with pathologically proven multiple system atrophy: a meta-analysis.

A systematic review of the neurologic literature identified 433 cases of pathologically proven multiple system atrophy over a 100-year period. Earlier case reports included patients younger in age with more frequent cerebellar involvement. Mean age of onset was 54.2 years (range 31 to 78) and survival was 6.2 years (range 0.5 to 24). Survival analysis showed a secular trend from a median duration of 4.9 years for publications between 1887 and 1970 to 6.8 years between 1991 and 1994. Older age of onset was associated with shorter survival; the hazard ratio for patients with onset after 60 years was 1.8 (95% CI 1.4 to 2.3) compared with patients between 31 and 49 years. Cerebellar features were associated with marginally increased survival (6.1 years versus 5.4 years; p = 0.04). There were no difference in survival according to gender, parkinsonian, or pyramidal features or whether the patient was classified as striatonigral degeneration or olivopontocerebellar atrophy type. These results demonstrate the poor prognosis for patients with multiple system atrophy but may be biased toward the worst cases. Future research needs to recruit more representative samples.

Adult↗