ABSTRACT
OBJECTIVE: It is known from neuropathological and imaging studies that the neuronal degeneration in Huntington's disease (HD) is already quite severe when the first symptoms of the disease become clinically evident. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the neurodegeneration in HD. METHODS: Motor cortex excitability was examined in 12 patients with HD in the early clinical stage of the disease and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, the short-interval paired-pulse intracortical inhibition (SICI) and the paired-pulse intracortical facilitation (ICF) were examined. RESULTS: The early-stage HD patients showed a statistically significant reduction in ICF. The other measures did not differ significantly from the control subjects. CONCLUSIONS: Our findings provide neurophysiological evidence that changes in motor function are present in the early HD. Since ICF is thought to depend upon the activity of intracortical glutamatergic excitatory circuits, the results of our study support the theory that altered NMDA receptor function plays an important role in the pathogenesis of HD. SIGNIFICANCE: These findings may provide clues to the underlying pathophysiology of the disease. A more complete understanding of the changes in motor cortex excitability that occur early in the course of HD will lead to a better definition of the disease process and may allow earlier diagnosis and intervention.
Subject(s)
Huntington Disease/physiopathology , Motor Cortex/physiopathology , Action Potentials/physiology , Adult , Disease Progression , Electromyography , Female , Glutamic Acid/physiology , Humans , Huntington Disease/genetics , Male , Middle Aged , Neural Conduction/physiology , Transcranial Magnetic StimulationABSTRACT
OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with restless legs syndrome (RLS) by administering the dopaminergic agonist cabergoline. METHODS: The effects of this drug on motor cortex excitability were examined with a range of transcranial magnetic stimulation (TMS) protocols before and after administration of cabergoline over a period of 4 weeks in 14 patients with RLS and in 15 healthy volunteers. Measures of cortical excitability included central motor conduction time; resting and active motor threshold to TMS; duration of the cortical silent period; short latency intracortical inhibition (SICI) and intracortical facilitation using a paired-pulse TMS technique. RESULTS: Short latency intracortical inhibition was significantly reduced in RLS patients compared with the controls and this abnormal profile was reversed by treatment with cabergoline; the other TMS parameters did not differ significantly from the controls and remained unaffected after treatment with cabergoline. Cabergoline had no effect on cortical excitability of the normal subjects. CONCLUSIONS: As dopaminergic drugs are known to increase SICI, our findings suggest that RLS may be caused by a central nervous system dopaminergic dysfunction. This study demonstrates that the cortical hyperexcitability of RLS is reversed by cabergoline, and provides physiological evidence that this dopamine agonist may be a potentially efficacious option for the treatment of RLS.
Subject(s)
Brain Diseases/complications , Brain Diseases/drug therapy , Ergolines/administration & dosage , Motor Cortex/drug effects , Restless Legs Syndrome/drug therapy , Restless Legs Syndrome/etiology , Adult , Aged , Brain Diseases/physiopathology , Cabergoline , Dopamine/metabolism , Dopamine Agonists/administration & dosage , Dopamine Agonists/adverse effects , Ergolines/adverse effects , Female , Humans , Male , Membrane Potentials/drug effects , Membrane Potentials/physiology , Middle Aged , Motor Cortex/metabolism , Motor Cortex/physiopathology , Neural Conduction/drug effects , Neural Conduction/physiology , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neurons/drug effects , Neurons/metabolism , Pyramidal Tracts/drug effects , Pyramidal Tracts/physiopathology , Reaction Time/drug effects , Reaction Time/physiology , Restless Legs Syndrome/physiopathology , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Transcranial Magnetic Stimulation , Treatment OutcomeABSTRACT
OBJECTIVE: Adults with Down syndrome (DS) develop progressive cognitive impairment resembling the cognitive profile of Alzheimer's disease (AD). Although the specific neurobiological correlates of cognitive deficits in DS are still not completely understood, it has been proposed that cholinergic dysfunction may contribute to some of these deficits in DS who develop AD. A recently devised test of motor cortex excitability, the short latency afferent inhibition (SAI), has been proven to be helpful in exploring some cholinergic circuits of the human brain. The authors used this test to assess the involvement of the cholinergic transmission in the DS. METHODS: We evaluated the SAI in 12 patients with DS and in 15 healthy subjects. RESULTS: SAI was significantly reduced in DS patients when compared with the controls; the values correlated with the patient's age and the score on Dementia Scale for Down Syndrome. SAI was increased after administration of a single dose of donezepil in a subgroup of 5 patients. CONCLUSIONS: Our findings suggest that, with respect to this putative marker of central cholinergic activity, dementia in aging DS shares pathophysiological similarities to AD in the general population. SIGNIFICANCE: This technique may help to clarify the pathophysiological basis of cognitive dysfunction in DS and may represent an additional tool for the diagnosis of Alzheimer-type dementia in subjects with DS.
Subject(s)
Alzheimer Disease/complications , Alzheimer Disease/physiopathology , Down Syndrome/complications , Down Syndrome/physiopathology , Neural Inhibition/physiology , Adult , Brain/drug effects , Brain/physiopathology , Cholinesterase Inhibitors/pharmacology , Donepezil , Female , Humans , Indans/pharmacology , Male , Middle Aged , Piperidines/pharmacology , Transcranial Magnetic StimulationABSTRACT
Congenital anomalies of the internal carotid arteries (ICA) and cerebral arteries have not been frequently reported. Moreover, in the literature there is no clear association between hypoplastic carotid and cerebral vessel systems and the occurrence of cerebral ischaemia. We report two cases of unilateral hypoplasia of the ICA affecting two young patients suffering from an episode of minor stroke and from recurrent transient ischaemic attacks, respectively. Congenital variations in the configuration and size of the carotid and cerebral arteries should not always be considered benign conditions and may predispose to cerebral ischaemia in young adults.
