Hans Speelman

Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection

Human immunodeficiency virus antigen (HIV-Ag) was detected in the serum of most adult (13/16) and paediatric (6/6) AIDS patients and rarely in the serum of symptomless seropositive controls (1/13). It was present in the cerebrospinal fluid (CSF) of all 5 children and most (5/9) adults with AIDS-related encephalopathy, but not in the CSF of 13 symptomless seropositive controls, of whom 8 had antibody in the CSF. A longitudinal study of 1 of the controls with antibody in the CSF showed that HIV-Ag in CSF was present transiently before the occurrence of antibody in the CSF. In serial samples of serum from 35 men who seroconverted HIV-Ag was detected in 11 persons--in 5 before seroconversion and in 6 after. 3 of the 6 who became antigenaemic after seroconversion remained so for the rest of the follow-up. AIDS was diagnosed in 1 patient, 3 months after HIV-Ag was first detected in serum and 6 months after seroconversion. The findings suggest that HIV-Ag appears early and transiently in primary HIV infection. Antibody production follows, after which HIV-Ag may disappear. Its persistence or reappearance seems to correlate with clinical, immunological, and neurological deterioration.

Declining incidence of AIDS dementia complex after introduction of zidovudine treatment

OBJECTIVE--To assess the incidence of the AIDS dementia complex and the presence of HIV I p24 antigen in cerebrospinal fluid in relation to zidovudine treatment. DESIGN--Retrospective study of a consecutive series of patients with AIDS from 1982 to 1988. SETTING--An academic centre for AIDS. PATIENTS--196 Patients with AIDS and neurological symptoms examined from 1982 to 1988. INTERVENTIONS--Zidovudine treatment, which was introduced to The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (Centers for Disease Control groups IVA, B, C, and D). MAIN OUTCOME MEASURES--Diagnosis of AIDS dementia complex and presence of HIV I p24 antigen in cerebrospinal fluid. RESULTS--The AIDS dementia complex was diagnosed in 40 of the 196 (20%) patients with AIDS. Thirty eight of 107 patients with AIDS (36%) not taking zidovudine developed the AIDS dementia complex compared with two of the 89 (2%) taking the drug (p less than 0.00001). The incidence of the AIDS dementia complex increased to 53% in the first half of 1987, after the introduction of zidovudine in May 1987, decreasing to 10% in the second half of 1987 and to 3% in 1988. Dementia was diagnosed before definition of the AIDS dementia complex (1986) according to DSM-III criteria and there was good agreement between diagnosis before and after 1986. Sixteen of 61 samples of cerebrospinal fluid (26%) from patients with AIDS (10 with the AIDS dementia complex) not taking zidovudine were positive for HIV I p24 antigen, whereas none of 37 cerebrospinal fluid samples from patients with AIDS (two with the AIDS dementia complex) taking zidovudine were positive. CONCLUSIONS--The incidence of AIDS dementia complex in patients with AIDS declined after the introduction of systematic treatment with zidovudine; the AIDS dementia complex might be prevented by inhibiting viral replication in the central nervous system.

The relationship between oscillatory activity and motor reaction time in the parkinsonian subthalamic nucleus.

Averaging techniques have demonstrated that movement preparatory cues and movement itself are associated with marked reductions in the oscillatory synchrony of local neuronal populations in the area of the human parkinsonian subthalamic nucleus (STN), as indexed by 8–30 Hz local field potential (LFP) activity. In order to examine the detailed nature and strength of the relationship between reductions in oscillatory activity and movement we examined single‐trial LFP activity recorded from the STN area of parkinsonian subjects engaged in a choice reaction task. In this task an initial warning cue was either fully predictive or non‐predictive of the hand required to make a later motor response. This motor response was elicited by a second go cue to which data were aligned. We observed a significant linear relationship between the onset time of oscillation reduction after go cues and subsequent motor response time across single trials within subjects. Consistent with this observation we also found a positive correlation of power with response time following go cues. In addition, we observed shorter durations of suppression in fully predictive trials where selection of the response could precede go cue presentation. The results are consistent with the hypothesis that reductions in 8–30 Hz population synchrony in the STN area are related to the processing required for motor preparation, particularly response selection.

Reciprocal interactions between oscillatory activities of different frequencies in the subthalamic region of patients with Parkinson's disease.

Synchronization of neuronal activity evident in the local field potential (LFP) recorded in the subthalamic region of patients with Parkinsons disease occurs at low frequencies (< 30 Hz) and, in some patients following treatment with levodopa, at high frequencies between 65 and 85 Hz. Here we investigate the functional relationship between these different activities by determining whether spontaneous fluctuations in their strength are correlated across time. To this end, we analysed recordings of LFPs from macroelectrodes inserted in the subthalamic area of 16 patients with Parkinsons disease, after treatment with anti‐parkinsonian medication. Time‐evolving autospectra of LFPs with significant 65–85 Hz peaks (from 21 sides) were computed and correlations between frequency components determined over time. LFP activity in the 5–32 Hz band was significantly negatively correlated with that in the 65–85 Hz band in data averaged across all 21 sides, as well as in 15 (71%) of the individual records. Negative correlations were relatively selective for interactions between these frequency bands and occurred over time epochs of as little as 40 s. They occurred about 50 min after levodopa and were recorded concurrently with contralateral levodopa‐induced dyskinesias in all but four cases. Positive correlations were not seen between activities in the 5–32 Hz and 65–85 Hz bands. The spontaneous negative correlations suggest a reciprocal relationship between population synchrony in the high‐ and low‐frequency ranges, and raise the possibility that spontaneous fluctuations in the balance between these activities may contribute to levodopa‐induced dyskinesias.

Effects of stereotactic neurosurgery on postural instability and gait in Parkinson's disease.

Postural instability and gait disability (PIGD) are disabling signs of Parkinsons disease. Stereotactic surgery aimed at the internal globus pallidus (GPi) or subthalamic nucleus (STN) might improve PIGD, but the precise effects remain unclear. We performed a systematic review of studies that examined the effects of GPi or STN surgery on PIGD. Most studies examined the effects of bilateral GPi stimulation, bilateral STN stimulation, and unilateral pallidotomy; we, therefore, only performed a meta‐analysis on these studies. Bilateral GPi stimulation, bilateral STN stimulation, and to a lesser extent, unilateral pallidotomy significantly improved PIGD, and more so during the ON phase than during the OFF phase.

Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Blink reflex recovery curves in blepharospasm, torticollis spasmodica, and hemifacial spasm.

R1 and R2 blink reflex responses to single and paired stimuli were investigated in 23 control subjects: 21 patients with blepharospasm (BSP), 20 patients with torticollis spasmodica (TS), and 23 with hemifacial spasm (HFS). For paired stimuli, we compared measurements of area and peak responses at two and three times R2 threshold. R1 and R2 indices were calculated as the average of the recovery values at 0.5‐, 0.3‐, and 0.21‐s interstimulus intervals to test individual patients. Peak amplitude measurements at three times R2 threshold were optimal. The R2 index was abnormal in 67% of BSP patients, 37% of TS patients, and 50% of HFS patients on the affected side and 20% on the unaffected side. A normal R2 index in one third of patients with BSP may indicate that different pathophysiological mechanisms are involved in this type of focal dystonia.

A Dutch family with 'familial cortical tremor with epilepsy' - Clinical characteristics and exclusion of linkage to chromosome 8q23.3-q24.1

Abstract.Objectives: To describe the clinical characteristics of a large Dutch family with cortical tremor with epilepsy (FCTE) and to test for genetic linkage of FCTE to chromosome 8q23.3–q24.1. Background: FCTE is an idiopathic generalised epilepsy of adult onset with autosomal dominant inheritance. It is characterised by kinesiogenic tremor and myoclonus of the limbs, generalised seizures, and electrophysiological findings consistent with cortical reflex myoclonus. Genetic analysis has been performed in five Japanese families. In all families, linkage was shown to chromosome 8q23.3–q24.1. Methods: Clinical and electrophysiological data of a four-generation family, suspected of autosomal dominant inherited FCTE, were collected and linkage analysis was performed. Results Clinical and electrophysiological findings were consistent with a diagnosis of FCTE. Of 41 relatives examined, 13 subjects were considered to be definitely affected, three were probably affected and ten were unaffected. In 15 relatives, the diagnosis could not be established. Linkage to chromosome 8q23.3–q24.1 was excluded. Conclusions: In this family with autosomal dominant FCTE, specific clinical and electrophysiological features were identified. Exclusion of linkage to chromosome 8q23.3–q24.1 indicates that genetic heterogeneity exists for FCTE.

Predictors of health care use in patients with Parkinson's disease : A longitudinal study

To predict health care use in patients with Parkinsons disease.

Distribution and Coexistence of Myoclonus and Dystonia as Clinical Predictors of SGCE Mutation Status: A Pilot Study

Introduction Myoclonus–dystonia (M–D) is a young onset movement disorder typically involving myoclonus and dystonia of the upper body. A proportion of the cases are caused by mutations to the autosomal dominantly inherited, maternally imprinted, epsilon-sarcoglycan gene (SGCE). Despite several sets of diagnostic criteria, identification of patients most likely to have an SGCE mutation remains difficult. Methods Forty consecutive patients meeting pre-existing diagnostic clinical criteria for M–D underwent a standardized clinical examination (20 SGCE mutation positive and 20 negative). Each video was reviewed and systematically scored by two assessors blinded to mutation status. In addition, the presence and coexistence of myoclonus and dystonia was recorded in four body regions (neck, arms, legs, and trunk) at rest and with action. Results Thirty-nine patients were included in the study (one case was excluded owing to insufficient video footage). Based on previously proposed diagnostic criteria, patients were subdivided into 24 “definite,” 5 “probable,” and 10 “possible” M–D. Motor symptom severity was higher in the SGCE mutation-negative group. Myoclonus and dystonia were most commonly observed in the neck and upper limbs of both groups. Truncal dystonia with action was significantly seen more in the mutation-negative group (p < 0.05). Coexistence of myoclonus and dystonia in the same body part with action was more commonly seen in the mutation-negative cohort (p < 0.05). Conclusion Truncal action dystonia and coexistence of myoclonus and dystonia in the same body part with action might suggest the presence of an alternative mutation in patients with M–D.