ABSTRACT
AIM: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular phenomenon recently described in multiple sclerosis (MS) that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. Aim of this study was to investigate the relationship between CCSVI and iron deposition in the brain of MS patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter structures and lesions, as measured by susceptibility-weighted imaging (SWI), and to preliminarily define the relationship between iron measures and clinical and other magnetic resonance imaging (MRI) outcomes. METHODS: Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI. RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume. CONCLUSION: The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS.
Subject(s)
Brain/metabolism , Iron/analysis , Jugular Veins/pathology , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Spinal Cord/blood supply , Venous Insufficiency/diagnosis , Adult , Atrophy , Brain/pathology , Case-Control Studies , Cerebrovascular Circulation , Chronic Disease , Constriction, Pathologic , Disability Evaluation , Female , Humans , Italy , Jugular Veins/physiopathology , Male , Multiple Sclerosis, Relapsing-Remitting/metabolism , Multiple Sclerosis, Relapsing-Remitting/pathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , New York , Pilot Projects , Predictive Value of Tests , Regional Blood Flow , Severity of Illness Index , Venous Insufficiency/metabolism , Venous Insufficiency/pathology , Venous Insufficiency/physiopathologyABSTRACT
Nitroglycerin has been widely used as a model of experimental migraine. Studies combining measurement of flow velocity using transcranial Doppler (TCD) concurrently with measures of cerebral blood flow (CBF) are uncommon. We report the results of a study combining TCD and positron emission tomography (PET). Healthy volunteers with no personal or family history of migraine underwent measurement of CBF using H215O PET, and velocity using TCD. Measurements were done at baseline, and following i.v. nitroglycerin at 0.125, 0.25 and 0.5 micro g/kg per min. Subcutaneous sumatriptan (6 mg) was injected, with CBF and velocity measured 15, 30, and 60 min later. Nitroglycerin was terminated and measurements obtained 30 min later. Six male and six female subjects were studied. Nitroglycerin increased global CBF while flow velocities decreased. Sumatriptan did not have a significant effect on these values. Regions of increased flow included the anterior cingulate, while regions of decreased flow included the occipital cortex. Our data suggest that nitroglycerin induces regional changes in CBF that are similar to changes reported in spontaneous migraine, but produces distinctly different effects on global CBF and velocity.
Subject(s)
Brain/blood supply , Brain/drug effects , Migraine Disorders/diagnostic imaging , Nitroglycerin/pharmacology , Tomography, Emission-Computed , Ultrasonography, Doppler, Transcranial , Adolescent , Adult , Blood Flow Velocity/drug effects , Blood Flow Velocity/physiology , Brain/diagnostic imaging , Female , Humans , Male , Middle Aged , Migraine Disorders/chemically induced , Tomography, Emission-Computed/methods , Ultrasonography, Doppler, Transcranial/methodsABSTRACT
The neural mechanisms involved in listening to sentences, and then detecting and verbalizing a specific word are poorly understood, but most likely involve complex neural networks. We used positron emission tomography to identify the areas of the human brain that are activated when young, normal hearing males and females were asked to listen to a sentence and repeat the last word from the Speech in Noise (SPIN) test. Listening conditions were (1) Quiet, (2) Speech, (3) Noise, and (4) SPIN with stimuli presented monaurally to either the left ear or the right ear. The least difficult listening task, Speech, resulted in bilateral activation of superior and middle temporal gyrus and pre-central gyrus. The Noise and SPIN conditions activated many of the same regions as Speech alone plus additional sites within the cerebellum, thalamus and superior/middle frontal gyri. Comparison of the SPIN condition versus Speech revealed additional activation in the right anterior lobe of the cerebellum and right medial frontal gyrus, near the cingulate. None of the left ear-right ear stimulus comparison revealed any significant differences except for the SPIN condition that showed greater activation in the left superior temporal gyrus for stimuli presented to the right ear. No gender differences were observed. These results demonstrate that repeating the last word in a sentence activates mainly auditory and motor areas of the brain when Speech is presented, whereas more difficult tasks, such as SPIN or multi-talker Noise, activate linguistic, attentional, cognitive, working memory, and motor planning areas.
Subject(s)
Auditory Pathways/diagnostic imaging , Auditory Pathways/physiology , Brain/diagnostic imaging , Brain/physiology , Speech Perception/physiology , Tomography, Emission-Computed , Adult , Brain Mapping , Cerebrovascular Circulation , Ear/physiology , Female , Functional Laterality/physiology , Humans , Male , Noise , Reference ValuesABSTRACT
OBJECTIVE: To identify neural sites associated with gaze-evoked tinnitus (GET), an unusual condition that may follow cerebellar-pontine angle surgery. METHODS: The authors examined eight patients with GET and used PET to map the neural sites activated by lateral gaze in them and seven age- and sex-matched control subjects. RESULTS: In patients with GET, tinnitus loudness and pitch increased with lateral gaze and, to a lesser extent, up and down gaze. Evidence for neural activity related to GET was seen in the auditory lateral pontine tegmentum or auditory cortex. GET-associated nystagmus appears to activate the cuneus and cerebellar vermis. These sites were found in addition to an extensive network that included frontal eye fields and other sites in frontal, parietal, and temporal cortex that were activated by lateral gaze in seven control subjects and the patients. The unilateral deafness in patients with GET was associated with expansion of auditory cortical areas responsive to tones delivered to the good ear. In addition to GET, unilateral deafness, end-gaze nystagmus, and facial nerve dysfunction were common. CONCLUSIONS: Patients with GET have plastic changes in multiple neural systems that allow neural activity associated with eye movement, including those associated with the neural integrator, to stimulate the auditory system. Anomalous auditory activation is enhanced by the failure of cross-modal inhibition to suppress auditory cortical activity. The time course for the development of GET suggests that it may be due to multiple mechanisms.
Subject(s)
Tinnitus/diagnostic imaging , Tinnitus/pathology , Adult , Brain/diagnostic imaging , Brain/pathology , Brain/physiopathology , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Tinnitus/physiopathology , Tomography, Emission-ComputedABSTRACT
Most functional imaging studies of the auditory system have employed complex stimuli. We used positron emission tomography to map neural responses to 0.5 and 4.0 kHz sine-wave tones presented to the right ear at 30, 50, 70 and 90 dB HL and found activation in a complex neural network of elements traditionally associated with the auditory system as well as non-traditional sites such as the posterior cingulate cortex. Cingulate activity was maximal at low stimulus intensities, suggesting that it may function as a gain control center. In the right temporal lobe, the location of the maximal response varied with the intensity, but not with the frequency of the stimuli. In the left temporal lobe, there was evidence for tonotopic organization: a site lateral to the left primary auditory cortex was activated equally by both tones while a second site in primary auditory cortex was more responsive to the higher frequency. Infratentorial activations were contralateral to the stimulated ear and included the lateral cerebellum, the lateral pontine tegmentum, the midbrain and the medial geniculate. Contrary to predictions based on cochlear membrane mechanics, at each intensity, 4.0 kHz stimuli were more potent activators of the brain than the 0.5 kHz stimuli.
Subject(s)
Auditory Pathways/physiology , Brain Mapping , Acoustic Stimulation , Adult , Animals , Audiometry , Cerebrovascular Circulation/physiology , Excitatory Postsynaptic Potentials , Female , Humans , In Vitro Techniques , Male , Nerve Net/physiology , Reference Values , Tomography, Emission-ComputedABSTRACT
We tested the hypothesis that tinnitus was due to excessive spontaneous activity in the central auditory system by seeking cerebral blood flow (CBF) changes that paralleled changes in the loudness of tinnitus in patients able to alter the loudness of their tinnitus. We found CBF changes in the left temporal lobe in patients with right ear tinnitus, in contrast to bilateral temporal lobe activity associated with stimulation of the right ear. The tones activated more extensive portions of the brain in patients than controls. We conclude that tinnitus is not cochlear in origin and associated with plastic transformations of the central auditory system. We suggest that tinnitus arises as a consequence of these aberrant new pathways and may be the auditory system analog to phantom limb sensations in amputees.
Subject(s)
Temporal Lobe/blood supply , Tinnitus/etiology , Auditory Diseases, Central/diagnosis , Auditory Diseases, Central/etiology , Humans , Neuronal Plasticity/physiology , Tinnitus/diagnosisABSTRACT
Do the brains of men and women show similar patterns of functional organization for language, or are men more strongly lateralized? We used PET to measure cerebral blood flow (CBF) as men and women read real and nonce verbs, and produced past tense forms. While the overall patterns of reaction time, error, and brain activation were similar, there were also significant sex-related differences in CBF patterns. During the past tense generation tasks, men showed left-lateralized activation while women recruited bilateral perisylvian cortex, confirming differences in functional laterality. During all tasks, women showed higher activation in occipital and/or cerebellar regions, suggesting differences in basic reading strategies. We conclude that sex differences in functional cortical organization exist in the absence of significant behavioral differences.
Subject(s)
Brain/physiology , Language , Reading , Adult , Female , Humans , Male , Sex CharacteristicsABSTRACT
We used PET to map brain regions responding to changes in tinnitus loudness in four patients who could alter tinnitus loudness by performing voluntary oral facial movements (OFMs). Cerebral blood flow was measured in four patients and six controls at rest, during the OFM, and during stimulation with pure tones. OFM-induced loudness changes affected the auditory cortex contralateral to the ear in which tinnitus was perceived, whereas unilateral cochlear stimulation caused bilateral effects, suggesting a retrocochlear origin for their tinnitus. Patients, compared with controls, showed evidence for more widespread activation by the tones and aberrant links between the limbic and auditory systems. These abnormal patterns provide evidence for cortical plasticity that may account for tinnitus and associated symptoms. Although audiologic symptoms and examinations of these patients were typical, the unusual ability to modulate tinnitus loudness with an OFM suggests some caution may be warranted in generalizing these findings.