ABSTRACT
BACKGROUND AND PURPOSE: To evaluate the effects of 25-Hz deep brain stimulation of the nucleus tegmenti pedunculopontini (PPTg) on brain metabolic activity. METHODS: Six patients with Parkinson's disease (PD) who had bilateral stereotactic implantation of PPTg at least 12 months prior to evaluation were included in our study. All underwent, in separate sessions, 18-FDG-PET in core assessment programme for intra-cerebral transplantation as well as motor evaluation [Unified Parkinson's disease rating scale (UPDRS)--Section III] and a battery of cognitive testing. RESULTS: PPTg-ON (low bipolar contacts, 25 Hz) promoted a significant increase of glucose utilization in bilateral prefrontal areas including dorsolateral prefrontal cortex (DLPFC, BA9), orbito-frontal cortex (BA47), anterior cingulate (BA 25-32), superior frontal gyrus (BA 10) and supramarginal gyrus (BA40); a significant increase of uptake and consumption of FDG also occurred in the left ventral striatum, left subgyral (BA 46), right insula (BA 13) and right superior temporal gyrus (BA 22). PPTg-ON was associated with a significant decrease of glucose utilization in the left cerebellar anterior lobe (culmen) and right cerebellar posterior lobe (declive). In the same patients, PPTg-ON improved delayed recall (P < 0.05) and executive functions whilst the UPDRS revealed a modest (-21%) and variable treatment effect. CONCLUSIONS: Low frequency stimulation of PPTg, a sub-region of the pedunculopontine nucleus complex, causes a minor motor benefit but a peculiar profile of cognitive improvement associated with a significant increase in FDG consumption in both prefrontal areas and mono-lateral ventral striatum. These data are consistent with multiple limbic and/or associative domains modulated by PPTg stimulation in our patients with PD.
Subject(s)
Deep Brain Stimulation/methods , Parkinson Disease/metabolism , Parkinson Disease/therapy , Pedunculopontine Tegmental Nucleus/physiology , Cerebellum/diagnostic imaging , Cerebellum/metabolism , Cognition Disorders/etiology , Cognition Disorders/metabolism , Cognition Disorders/therapy , Energy Metabolism/physiology , Female , Glucose/metabolism , Humans , Male , Neuropsychological Tests , Parkinson Disease/diagnostic imaging , Pedunculopontine Tegmental Nucleus/metabolism , Positron-Emission Tomography/methods , Stereotaxic Techniques , Treatment OutcomeABSTRACT
OBJECTIVE: To perform a clinical and genetic study of two large Italian families (RM-36 and RM-51) showing the cardinal clinical features of Silver syndrome (SS), a rare dominantly inherited form of hereditary spastic paraplegia (HSP) complicated by amyotrophy of the small hand muscles. METHODS: Clinical assessment including neurophysiologic, neuropsychological, and neuroimaging evaluations. Genetic studies included linkage and sequence analyses. RESULTS: Using a genome-wide survey in the RM-36 family, a novel locus (SPG38) has been identified and mapped within the 13.1-cM region on chromosome 4p16-p15 between markers D4S432 and D4S1599. The RM-51 family was linked to the SPG4 locus at 2p21-p24 and sequence analysis of SPG4 showed a novel frameshift mutation p.Asp321GlyfsX6. Clinical examination of the affected members carrying the mutation showed high frequency of additional clinical features including decreased vibration sense, pes cavus, temporal lobe epilepsy, and cognitive impairment. CONCLUSIONS: This study demonstrates evidence of a novel locus SPG38 for Silver syndrome (SS) and suggests that genetic defects in SPG4 might lead to broad clinical features overlapped with those of SS.
Subject(s)
Adenosine Triphosphatases/genetics , Alleles , Lod Score , Spastic Paraplegia, Hereditary/genetics , Spastic Paraplegia, Hereditary/pathology , Adolescent , Adult , Cognition Disorders/genetics , Cognition Disorders/pathology , Electromyography , Epilepsy, Temporal Lobe/genetics , Epilepsy, Temporal Lobe/pathology , Family Health , Female , Genes, Dominant , Genomics , Humans , Magnetic Resonance Imaging , Male , Neural Conduction , Pedigree , Phenotype , Spastic Paraplegia, Hereditary/physiopathology , SpastinABSTRACT
OBJECTIVE: To compare acute and chronic effects of l-dopa on bladder function in levodopa-naive Parkinson disease (PD) patients who had urinary urgency. METHODS: We evaluated 26 l-dopa-naive PD patients at a university-based PD center with a first urodynamic session with a double examination: in the off treatment condition and 1 hour after acute challenge with carbidopa/l-dopa 50/200 mg; then, a chronic l-dopa monotherapy was administered (mean dose 300 +/- 150 mg). Two months later, patients underwent a second urodynamic session with a single evaluation 1 hour after the acute carbidopa/l-dopa challenge. RESULTS: The first acute l-dopa challenge significantly worsened bladder overactivity (neurogenic overactive detrusor contractions threshold [NDOC-t; 32% of worsening] and bladder capacity [BC; 22% of worsening]); on the contrary, l-dopa challenge during chronic administration ameliorated the first sensation of bladder filling (FS; 120% of improvement), NDOCT-t (93% improvement), and BC (33% of improvement) vs the values obtained with acute administration. An 86% significant improvement of FS in comparison with the basal value was observed. CONCLUSIONS: The acute and chronic l-dopa effects may be due to the different synaptic concentrations or to the activation of postsynaptic mechanisms obtained by chronic administration.
