Economic burden and quality of life impairment increase with severity of PD.

PURPOSE: To define the interrelationship between cost-of-illness, quality of life (QoL) and Parkinson's disease (PD) severity in a common patient management setting in Finland.Scope. Two hundred and sixty consecutive outpatients with idiopathic PD participated. UPDRS, motor fluctuations, QoL, and the use of health care resources were measured. Direct and indirect costs were calculated. CONCLUSIONS: There is a strong relationship between QoL or cost-of-illness on the one hand, and severity of PD on the other. Treatment policies capable of reducing or delaying motor fluctuations would be expected to increase QoL and reduce some of the economic burden of PD.

Late onset foot-drop muscular dystrophy with rimmed vacuoles.

We studied a family with late-onset (fifth or sixth decade) or asymptomatic hereditary myopathy of the anterior tibial muscle. The occurrence of the disease in two successive generations pointed out an autosomal dominant pattern of inheritance. The initial symptom was uni- or bilateral foot drop resembling peroneal paresis. Surprisingly many of the diagnosed patients were asymptomatic and considered themselves healthy whether there was any foot drop or not. The anterior tibial muscles were atrophic in patients with foot drop but the long toe extensors were usually and the short ones were always spared. Apparently the toe extensors could relieve the foot drop symptom. As shown by computed tomography there was often an early uni- or bilateral involvement of the semimembranosus muscle in males. The proband showed also a late involvement of the femoral biceps and the minor gluteal muscles. The muscles of the upper extremity were spared. The anterior tibial muscles had a characteristic myopathic alteration with rimmed vacuoles in histopathological study. This picture was most evident in latent cases without atrophy of the anterior tibial muscle, but with distinctly abnormal EMG of that muscle. Non-affected muscles showed only slight non-specific histopathological changes. We suggest that this disease is a new mild variety of autosomal dominant distal myopathy with rimmed vacuoles.

Initial experience with single-photon emission tomography using iodine-123-labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane in human brain.

The iodinated cocaine analogue 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT), a new dopamine transporter, was preliminary tested in human brain. Two normal volunteers and two patients with Parkinson's disease were imaged with a high-resolution single-photon emission tomography scanner. The specific binding of [123I]beta-CIT in the basal ganglia and thalamus was high in normal volunteers. In addition, there was relatively intense uptake in the medial prefrontal area. Patients with Parkinson's disease who were older than controls showed significantly lower specific binding in the basal ganglia and thalamus and no uptake in the medial prefrontal cortex. This decrease in the dopamine transporter may be age related.

Tibial muscular dystrophy. Late adult-onset distal myopathy in 66 Finnish patients.

OBJECTIVE: To clarify the classification of two previously reported groups of patients with anterior tibial distal dystrophy, to find additional patients with the disease, and to describe the clinical features of this disease. DESIGN: National survey of the records of patients with neuromuscular diseases in Finland. Findings of selected patients were compared with those of previously reported cases. PATIENTS: Thirty-six previously described patients and 30 additional patients from the current survey, with 41 symptomatic patients and 25 subjectively asymptomatic affected relatives. RESULTS: There were 66 patients with late adult-onset tibial muscular dystrophy. Symptoms appear after the age of 35 years with reduced ankle dorsiflexion, and progress is slow without marked disability. Facial muscles, upper extremities, and proximal muscles are usually spared. Muscle biopsy results reveal nonspecific dystrophic changes in clinically affected muscles, and frequently severe adipose replacement in the anterior tibial muscles occurs. Asymptomatic muscles have mild myopathic changes only. Vacuolar degeneration is detected in a minority of patients. Electromyography shows profound myopathic changes in the anterior tibial muscle, but extensor brevis muscles are well preserved. Computed tomography or magnetic resonance imaging of muscles discloses marked involvement of tibial extensor muscles and focal patches of fatty degeneration in various asymptomatic muscles. Pedigree data suggest autosomal dominant inheritance. CONCLUSIONS: Tibial muscular dystrophy might represent a new form of distal myopathy and it is rather common, at least in Finland.

Imaging of D2 dopamine receptors of patients with Parkinson's disease using single photon emission computed tomography and iodobenzamide I 123.

OBJECTIVE: To test the usefulness of single photon emission computed tomography (SPECT) with iodobenzamide in imaging basal ganglia and to elucidate the postulated upward regulation of the striatal D2 dopamine receptors in patients with early Parkinson's disease. DESIGN: Fourteen patients with Parkinson's disease and eight control subjects were investigated with SPECT using iodobenzamide labeled with iodine 123 as dopamine receptor ligand. SETTING: Neurological outpatient service at a university hospital in Kuopio, Finland. PATIENTS: Fourteen patients with recently diagnosed unilateral, unmedicated Parkinson's disease and eight healthy control subjects. RESULTS: The SPECT images revealed high uptake of iodobenzamide in the basal ganglia. In the patient group, the accumulation was more intense and the iodobenzamide affinity rate was significantly higher in the striatum contralateral to the parkinsonian symptoms. Also, the basal ganglia-cerebellum ratio was higher in the contralateral hemisphere. In the control group, no significant side-to-side differences were observed. CONCLUSION: Iodobenzamide with SPECT imaging is useful in evaluating patients with Parkinson's disease. The results also suggest compensatory D2 dopamine receptor upward regulation in the striatum of patients with early unmedicated Parkinson's disease.

Extrapyramidal signs in Alzheimer's disease: a 3-year follow-up study.

Occurrence of extrapyramidal signs was investigated in a follow-up study of 32 patients with probable Alzheimer's disease (AD). Bradykinesia and rigidity were observed in 39% and 11% of the neuroleptic-free patients at entry and in 72% and 61% at year 3, respectively. Tremor was not a predominant feature nor did its occurrence increase over time. Use of neuroleptics contributed to extrapyramidal signs; 75-100% of the neuroleptic-treated patients showed bradykinesia, rigidity or orofacial dyskinesia. The homovanillic acid (HVA) concentrations of the cerebrospinal fluid at entry were comparable to those of age-matched controls. Nor did HVA levels correlate with rigidity or bradykinesia in these early AD cases. Presence of bradykinesia or rigidity at the initial evaluation predicted more severe dementia and a poor prognosis over the period of 3 years, although interaction of initial clinical severity of dementia was significant. Of 15 patients with these signs 3 (20%) died and 8 (53%) needed institutional care, while of 17 patients without these signs only 1 (6%) died and 2 (12%) were institutionalized by year 3 (p less than 0.01).

Cognitive profile of Alzheimer patients with extrapyramidal signs: a longitudinal study.

The cognitive profile of Alzheimer patients without (ADE-, n = 17) and with (AD, E+, n = 15) extrapyramidal signs (rigidity or bradykinesia), at the time of diagnosis, was examined in a 3-year follow-up study and compared to cognitive performance of demented (PD D+, n = 18) and nondemented (PD D-, n = 17) patients with Parkinson's disease and normal elderly controls (n = 19). Although the AD E+ and AD E- groups did not differ significantly at the initial testing, the AD E+ patients showed greater deterioration on visual, praxic and expressive speech functions as well as in category memory. The cognitive profile of the AD E+ patients was similar to that of the PD D+ patients except that the AD E+ patients recognized more false positive targets on list-learning task. The AD E- patients had better preserved praxic functions and WAIS Performance IQ but they, like AD E+ patients, recognized more false positive targets on list-learning than the PD D+ patients did. The results suggest that AD patients with extrapyramidal signs, even if mild, at the time of diagnosis may have greater progression of cognitive impairment, especially on cortical functions, which may explain earlier need for institutional care observed in previous studies as compared to patients without these signs.

Serial EEG in Alzheimer's disease: 3 year follow-up and clinical outcome.

We describe EEG findings and clinical outcomes of 24 Alzheimer (AD) patients over a 3 year follow-up period. Three records, baseline, 1 year and 3 year, were available for 13 patients. Although the majority of the patients showed slowing of the EEG over 3 years, evolutions of the EEG changes were not equal in all patients. In 12 (50%) of the patients the EEG from T6-O2 derivation was normal or slightly abnormal in the initial record and remained stable during 1 year. At year 3, only 2 patients still had normal EEGs and mild dementia, probably representing a subgroup of AD with a benign course, 7 patients needed institutional care and 3 had died. EEG slowing at the time of diagnosis was predictive of poor outcome at year 3; absolute theta amplitude was the best discriminating variable of outcome. The results support the idea of heterogeneity of AD patients and suggest that EEG may provide valuable information for prediction of outcome.

Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease.

Cortical functions and slow-wave activity in the spectral analysis of the electroencephalogram (EEG) have been studied in 19 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease with dementia (PD), and 14 control subjects (C) to determine which functions are explained by their relationship of slow-wave activity. Multiple regression analyses revealed that a variance in visual functions, praxia of the hand, automatic speech, speech understanding, and retrieval from semantic memory were explained by their relationship with slow-wave activity in EEG in the AD group but not in the PD or C groups. The PD and AD groups exhibited equal cortical dysfunctions and mean amplitudes of delta activity in EEG. The cholinergic system, disrupted in AD, has been shown to be important in the regulation of neocortical electrical activity and may be associated with the processing of cortical functions.

Discrimination of tetrahydroaminoacridine responders by a single dose pharmaco-EEG in patients with Alzheimer's disease.

We report the results of our study suggesting that a single dose pharmaco-EEG may predict treatment response to tetrahydroaminoacridine (THA) in Alzheimer's disease (AD). 14 AD patients and 7 age-matched neurologically healthy controls were selected for the study. AD patients had 7 weeks' THA treatment. 6 patients were regarded as responders and 8 patients as nonresponders, respectively. AD patients as well as controls had a baseline EEG recording and next day another recording 90 minutes after a peroral single dose of 50 mg THA. The relative change from the baseline in the alpha-theta ratio was the most sensitive discriminator of responders and nonresponders (P = 0.004, ANOVA).

Different patterns of cognitive decline related to normal or deteriorating EEG in a 3-year follow-up study of patients with Alzheimer's disease.

To determine if the pattern of cognitive decline in Alzheimer's disease (AD) patients with normal EEG differs from that in patients with abnormal EEG at the early stage of the disease, we have followed 12 AD patients with normal EEG (NEEG) and 12 patients with deteriorating EEG (DEEG). The AD patients with DEEG showed a decline of praxic functions, confrontation naming, and automatic speech functions. In contrast, the AD patients with NEEG did not show a deterioration of these functions during the 3-year follow-up period. Visual functions, understanding of speech, and memory functions deteriorated similarly in both groups. The clinical severity of dementia increased in both groups. Patients with DEEG showed a tendency toward a higher frequency of extrapyramidal symptoms and a higher risk of institutionalization than the patients with NEEG. Thus, an abnormal EEG at the early stage of AD may predict a more severe decline in cognitive functions.

Benign muscular dystrophy with autosomal dominant inheritance.

A slowly progressive myopathy was discovered in a family in four successive generations. Eight patients (four female, four male) from three generations were examined and they showed muscle weakness affecting predominantly proximal, but also distal, muscles. Two patients had unequivocal findings in childhood, the others showed myopathy in their twenties or thirties. Working ability was lost in physically demanding jobs in the thirties, but activities of daily living were still preserved. Elbow contractures, tight heel cords and contractures of the interphalangeal joints were frequent. Serum CK activity was usually mildly elevated and electromyographic examinations revealed myopathic changes. Histopathological changes were compatible with moderately advanced muscular dystrophy in two patients, the six others had mild myopathic changes.

Longitudinal EEG spectral analysis in early stage of Alzheimer's disease.

Twenty-four patients with mild to moderate Alzheimer's disease (AD) were studied using quantitative spectral analysis of EEG at the time of the diagnosis and 1 year later. In 50% of the patients EEG spectra from the T6-O2 derivation were either normal or mildly abnormal at baseline and did not change at 1 year. In another half of the patients the mean quantitative EEG variables (the alpha and the delta power and the mean frequency) deteriorated significantly when baseline and 1 year values were compared. The patient groups with deteriorating and stable EEGs did not differ in age, sex, age at onset or duration of the disease or clinical severity at baseline or at 1 year. Dementia also progressed significantly in both subgroups of AD patients. We conclude that even if the mean values of quantitative EEG variables analysed from the T6-O2 derivation showed distinct slowing at the time of the AD diagnosis and further deterioration 1 year later, in 50% of these early AD cases there was no EEG alteration or worsening in 1 year follow-up, suggesting heterogeneity of the disease.

Different error pattern of episodic and semantic memory in Alzheimer's disease and Parkinson's disease with dementia.

To evaluate the possible differences in memory dysfunction we analysed the episodic and semantic memory of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) with dementia, and age-matched normal controls (NC). The memory was examined with story recall tests, list learning test with Buschke selective reminding method and category naming test. Both AD and PD groups committed more prior-story intrusion errors as compared with the NC subjects, but only the AD patients committed more extra-story intrusion errors. Both patient groups committed more extra-list intrusion errors than the NC group. Furthermore, the AD patients made more extra-list intrusion errors and recognized more false positive targets than the PD patients did. The results suggest that AD and PD patients have different patterns of memory dysfunction. The AD patients seem to perform poorly because of their inability to inhibit irrelevant information and because of increased sensitivity to interference, whereas the deficits of PD patients only reflect sensitivity to proactive interference.

Recall and recognition memory in patients with Alzheimer's and Parkinson's diseases.

Alzheimer's and Parkinson's diseases are associated with cognitive impairment, although the pattern of cognitive dysfunction is not identical. We investigated the recall and recognition memory of 18 patients with idiopathic Parkinson's disease (PD) and of 32 patients with probable Alzheimer's disease (AD). In the list-learning test using Buschke's selective reminding method, PD patients showed superior delayed recognition memory capability compared to AD patients, whereas immediate recall did not differ in the two groups. In the delayed story recall, PD patients were also able to benefit from rehearsal and probe more than AD patients. The results suggest that PD patients are able to bind information better into long-term storage than are AD patients. This may be due to better function in PD of the entorhinal cortex and hippocampus.

Peripheral neuropathy in late onset spinocerebellar ataxia.

We studied 10 patients with late onset spinocerebellar ataxia including electrophysiological and muscle biopsy examinations. Nerve conduction studies of eight patients revealed axonal neuropathy, and six cases also showed signs of the involvement of the lower motor neuron. In 9 patients quantitative analysis of single motor unit potentials (MUPs) of the tibialis anterior or biceps brachii muscles showed mild to severe neuropathic changes and in all 10 patients the histopathological examination of the tibialis anterior showed mild to severe neuropathic changes. Neither nerve conduction studies, quantitative MUP analysis, nor histological findings of the muscle were related to the severity of duration of the disease.

Cerebrospinal fluid somatostatin correlates with spectral EEG variables and with parietotemporal cognitive dysfunction in Alzheimer patients.

Somatostatin levels of the cerebrospinal fluid (CSF) were correlated with variables of quantitative EEG and with neuropsychological performance in patients with probable Alzheimer's disease. Low somatostatin levels of CSF correlated with decreased beta activity and with decreased mean frequency in the combined alpha and theta EEG range. In the subgroup of mild Alzheimer cases CSF somatostatin correlated positively also with alpha power, and the peak and the mean frequency, and negatively with theta power but not with delta activity. Furthermore, low somatostatin of the CSF correlated with neuropsychological tests assessing temporoparietal dysfunction. To our knowledge, this is the first study to indicate the correlation between spectral analysis results of the EEG and CSF somatostatin suggesting that the relationship between somatostatin and EEG variables is worthy of further studies.