Prenatal and early postnatal environments can permanently influence health throughout life. Early overnutrition increases the risk to develop chronic diseases. Conversely, the intake of flavonoids and exercise practice during pregnancy seem to promote long-term benefits to offspring. We hypothesized that benefic interventions during pregnancy could protect against possible postnatal neurochemical alterations caused by overnutrition induced by reduced litter size. Female Wistar rats were divided into four groups: (1) sedentary + vehicle, (2) sedentary + naringenin, (3) swimming exercise + vehicle, and (4) swimming exercise + naringenin. One day after birth, the litter was culled to 8 pups (control) or 3 pups (overfed) per dam, yielding control and overfed subgroups for each maternal group. Serum of 21-days-old pups was collected, also the cerebellum, hippocampus, and hypothalamus were dissected. Litter size reduction increased fat mass and enhanced body weight. Maternal interventions, when isolated, caused reduced glucose serum levels in offspring nurtured in control litters. In the cerebellum, reducing the litter size decreased the activity of thioredoxin reductase, which was prevented by maternal supplementation with naringenin. Hippocampus and hypothalamus have shown altered antioxidant enzymes activities in response to litter size reduction. Interestingly, when maternal exercise and naringenin supplementation were allied, the effect disappeared, suggesting a concurrent effect of the two maternal interventions. In conclusion, exercise or naringenin supplementation during pregnancy can be important interventions for combating the increasing rates of overweight during the infancy and its related neurochemical changes, especially when applied isolated.
Transplanted bone marrow-derived cells (BMDCs) have been reported to fuse with cells of diverse tissues, but the extremely low frequency of fusion has led to the view that such events are biologically insignificant. Nonetheless, in mice with a lethal recessive liver disease (tyrosinaemia), transplantation of wild-type BMDCs restored liver function by cell fusion and prevented death, indicating that cell fusion can have beneficial effects. Here we report that chronic inflammation resulting from severe dermatitis or autoimmune encephalitis leads to robust fusion of BMDCs with Purkinje neurons and formation of hundreds of binucleate heterokaryons per cerebellum, a 10-100-fold higher frequency than previously reported. Single haematopoietic stem-cell transplants showed that the fusogenic cell is from the haematopoietic lineage and parabiosis experiments revealed that fusion can occur without irradiation. Transplantation of rat bone marrow into mice led to activation of dormant rat Purkinje neuron-specific genes in BMDC nuclei after fusion with mouse Purkinje neurons, consistent with nuclear reprogramming. The precise neurological role of these heterokaryons awaits elucidation, but their frequency in brain after inflammation is clearly much higher than previously appreciated.
Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially alpha-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly alpha-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. alpha-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.
Radical resection of VII nerve schwannomas classically implies a high risk of severe facial palsy. Due to the rarity of facial palsy after Gamma Knife surgery (GKS) of vestibular schwannomas the evaluation of GKS in this specific difficult group of patient appears rational. We have found no similar evaluation in the literature. Among 1.000 schwannomas of the cerebello-pontine angle operated in Marseilles, France between July 1992 and March 2003, 9 have been diagnosed as originating from the VII. Criterias for this diagnosis are the involvement of the second or third portion of the VII nerve canal (7 patients) and/or peroperative observation during a previous microsurgery (2 patients). The rare facial palsy after vestibular schwannomas radiosurgery occurring usually before 18 Months have been considerated only the patients with more than 2 Years of follow-up (8 patients). Four of these patients had the experience of a previous spontaneous facial palsy one (3 patients) or several times (1 patient). A normal motor facial function was observed only in 2 cases before GKS (House 2 in 6 patients, House 3 in one). The follow-up was 2-7 Years for the evaluable patients. None of these have developed or worsened facial palsy, two have improved their preoperative facial palsy. To date, all tumors have been evaluated. The specificity and heterogeneity of this group of patients led us to develop an original classification in 4 anatomical types presenting different clinical and surgical difficulties. This first study demonstrates that radiosurgery allows treating these patients while preserving a normal motor facial function. Because of this advantage, GKS must be considered as a first option for all small to middle sized facial nerve schwannomas.
We recently used a differential display PCR screen to identify secreted and transmembrane proteins that are highly expressed in the developing rat basilar pons, a prominent ventral hindbrain nucleus used as a model for studies of neuronal migration, axon outgrowth, and axon-target recognition. Here we describe cloning and characterization of one of these molecules, now called MDGA1, and a closely related homologue, MDGA2. Analyses of the full-length coding region of MDGA1 and MDGA2 indicate that they encode proteins that comprise a novel subgroup of the Ig superfamily and have a unique structural organization consisting of six immunoglobulin (Ig)-like domains followed by a single MAM domain. Biochemical characterization demonstrates that MDGA1 and MDGA2 proteins are highly glycosylated, and that MDGA1 is tethered to the cell membrane by a GPI anchor. The MDGAs are differentially expressed by subpopulations of neurons in both the central and peripheral nervous systems, including neurons of the basilar pons, inferior olive, cerebellum, cerebral cortex, olfactory bulb, spinal cord, and dorsal root and trigeminal ganglia. Little or no MDGA expression is detected outside of the nervous system of developing rats. The similarity of MDGAs to other Ig-containing molecules and their temporal-spatial patterns of expression within restricted neuronal populations, for example migrating pontine neurons and D1 spinal interneurons, suggest a role for these novel proteins in regulating neuronal migration, as well as other aspects of neural development, including axon guidance.
The aim of this study was to assess tolerance and efficacy of gamma knife radiosurgery on vestibular schwannomas for patients affected with neurofibromatosis type 2. Between July 1992 and December 1997, a gamma knife procedure was performed on 35 vestibular schwannomas affecting 27 patients (12 females and 15 males, mean age=27 years-old, range: 14-65). Fifteen of the patients were included in the Wishart subtype (severe form) and 12 patients in the Gardner subtype (mild form). This group of 27 patients represented 8,2% of the total group of vestibular schwannomas radiosurgically treated by our team. The mean tumor volume was 4,000 mm(3) (range: 400-14,400 mm(3)) and staging according to Koos classification was 9 stage 2 tumors (extension in the cerebellopontine angle), 19 stage 3 tumors (in contact with the brain stem or cerebellum) and 7 stage 4 tumors (compression of axial structures). The delivered mean marginal dose (50% isodose) was 13 Gy (range: 10-18 Gy). After the treatment, the mean clinical and radiological follow-up was 32 months (range: 6-70). Twenty six (74%) of the treated tumors were controlled by the treatment (15 stabilizations and 11 regressions of the tumor volume) at last follow-up. One microsurgical removal was required in a growing stage 4 tumor and in 2 cases of growing stage 3 tumors. Three post-radiosurgical facial nerve deficits (9%) were observed, 2 of them were transient. According to the Gardner and Robertson classification, classes I (good) and II (serviceable) hearing were preserved at last follow-up in 57% of the patients having the same hearing level prior to the gamma knife. Our experience confirms that tolerance of gamma knife radiosurgery compares favorably with microsurgery of bilateral vestibular schwannomas. This treatment should be restricted to small and medium growing tumors. Treatment strategy of neurofibromatosis type 2 patients should be planned by multidisciplinary experienced teams disposing of the whole armamentarium. A longer follow-up study is required to confirm the current results regarding the tumor control rate.
A case of cauda equina paraganglioma is described; subsequent intracranial and intraspinal metastases occurred after partial resection and adjunctive radiotherapy. Cerebrospinal fluid dissemination is a rare complication of spinal paragangliomas. Factors predictive of this unusual biological behaviour are discussed.
A 32-year-old woman presented with increasing motor difficulties and memory disturbances. Neurological examination only showed mild cerebellar and extrapyramidal symptoms, whereas neuropsychological evaluation disclosed severe cognitive changes consistent with dementia. Her motor and mental status progressively deteriorated until death, which occurred 5 years after the first admission. One year before death, while she was almost bedridden, symptoms of myoclonic epilepsy first appeared, with frequent generalized seizures and generalized myoclonus, occurring especially upon sensory stimulation or passive joint movements. Pathological examination showed neuronal inclusions typical of Kufs' disease. This case, with primary progressive dementia and late-onset myoclonic epilepsy, differs from previously reported cases. Three special electrophysiological features were abnormal, "giant", evoked potentials; unusually marked photosensitivity; and seizure induction by any sensory stimulation.
We report a primary histiocytic tumor involving the cerebellum. Microscopically, the tumor was composed of nests of pleomorphic cells surrounded by thin vascular septa invaded by lymphocytes. Immunocytochemistry and electron microscopy confirmed the histiocytic origin of the tumor. Although we considered several diagnoses, we ultimately concluded that "atypical inflammatory histiocytic tumor of the cerebellum" best characterized the lesion. This case represents another example of the diversity of histiocytic tumors and shows that they can occur in the central nervous system.
1. A cat, restrained in a hammock, stands with its feet on supporting trays each furnished with strain gauges to measure the isometric upthrust. Placing reactions are elicited by contact of the left or right forelimb with a moving tray. The placing movement is preceded and accompanied by a postural adjustment characterized by an increase of the upthrust exerted by the opposite forelimb. 2. After ablation of the motor cortex on one side, the placing movement of the contralateral forelimb is abolished for the first few days after the operation and thereafter is delayed. However, the postural adjustment of the ipsilateral forelimb persists, with the same range of latencies as before the operation. 3. After unilateral motor cortical ablation, the contralateral forelimb still takes part in the postural adjustment associated with the placing movement of the other forelimb. 4. In two cats which had 2 years earlier undergone a total cerebellectomy, the placing movement was lacking or appeared with a long delay, whereas a postural adjustment of the other forelimb could be observed, although reduced. 5. The results indicate that the nervous structures responsible for the movement and for the associated postural adjustment are separate but partially linked.
The term rhombencephalitis refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum). Rhombencephalitis has a wide variety of etiologies, including infections, autoimmune diseases, and paraneoplastic syndromes. Infection with bacteria of the genus is the most common cause of rhombencephalitis. Primary rhombencephalitis caused by infection with spp. occurs in healthy young adults. It usually has a biphasic time course with a flu-like syndrome, followed by brainstem dysfunction; 75% of patients have cerebrospinal fluid pleocytosis, and nearly 100% have an abnormal brain magnetic resonance imaging scan. However, other possible causes of rhombencephalitis must be borne in mind. In addition to the clinical aspects, the patterns seen in magnetic resonance imaging can be helpful in defining the possible cause. Some of the reported causes of rhombencephalitis are potentially severe and life threatening; therefore, an accurate initial diagnostic approach is important to establishing a proper early treatment regimen. This pictorial essay reviews the various causes of rhombencephalitis and the corresponding magnetic resonance imaging findings, by describing illustrative confirmed cases. O termo rombencefalite se refere a doenças inflamatórias que afetam o rombencéfalo (tronco cerebral e cerebelo). Rombencefalites possuem grande variedade de causas, incluindo infecciosas, autoimunes e síndromes paraneoplásicas. é a causa mais comum das rombencefalites infecciosas. A rombencefalite primária por ocorre em adultos jovens e saudáveis, com um curso de tempo bifásico, como uma síndrome gripal acompanhada de disfunção do tronco cerebral. Em 75% dos pacientes manifesta-se pleiocitose no líquido cefalorraquidiano e em quase 100% a ressonância magnética cerebral é anormal. Mas há outras causas possíveis para rombencefalites que devem ser lembradas. Além de aspectos clínicos, os padrões de imagem encontrados na ressonância magnética podem ser úteis na definição da possível causa. Algumas das causas descritas de rombencefalites são potencialmente graves e fatais; assim, uma abordagem diagnóstica inicial precisa é importante para estabelecer um tratamento precoce adequado. Este ensaio iconográfico revisa as diversas causas de rombencefalites e os seus achados de ressonância magnética, por meio de casos ilustrativos confirmados.
As cortical microbleeds and microinfarcts in neurodegenerative and cerebrovascular diseases have been studied predominantly at the level of the cerebral hemispheres and linked to the presence of cerebral amyloid angiopathy (CAA), we aimed at determining with 7.0-tesla magnetic resonance imaging (MRI) whether the causes and the frequency of cortical cerebellar microbleeds (CCeMBs) and microinfarcts (CCeMIs) are the same. Hundred and four postmortem brains, composed of 29 with pure Alzheimer's disease (AD), 9 with AD associated to CAA, 10 with frontotemporal lobar degeneration, 9 with amyotrophic lateral sclerosis, 10 with Lewy body disease, 12 with progressive supranuclear palsy, 9 with vascular dementia (VaD), and 16 controls, were examined. On a horizontal section of a cerebellar hemisphere examined with 7.0-tesla MRI, the number CCeMBs and CCeMIs were compared between the different disease groups and the control group. The MRI findings were also compared with the corresponding mean values observed on histological examination of a separate standard horizontal section of a cerebellar hemisphere, used for diagnostic purpose. CCeMBs and CCeMIs were only significantly increased in the VaD group. When comparing the diseased patients with and without CAA mutually and with those with arterial hypertension and severe atherosclerotic cerebrovascular disease, only in the latter an increase of CCeMBs and CCeMIs was observed. There was an excellent correlation between the MRI and the neuropathological findings. CCeMBs and CCeMIs are mainly due to atherosclerotic cerebrovascular disease and not due to CAA. Their increased presence cannot be included to the Boston diagnostic criteria for CAA.
Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) has been associated with the development of postoperative apathy. Debate on the causes of postoperative apathy continues, and the dominant hypothesis is that stimulation or dopaminergic drug reductions are causal in its development. We hypothesized that a preoperative predisposition to apathy also could exist. To this end, we sought to identify a preoperative metabolic pattern using [(18)]Fluorodeoxyglucose Positron Emission Tomography (PET), which could be associated with the occurrence of postoperative apathy after STN-DBS for PD. Thirty-four patients with PD, not clinically apathetic, underwent an [(18)]Fluorodeoxyglucose-PET scan before surgery of STN-DBS, and were tested for the occurrence of apathy 1 y after surgery. Whole-brain voxel-based PET intergroup comparison (P < 0.005; corrected for the cluster) was evaluated between patients who developed apathy at 1 y and those who did not. Eight patients (23.5%) became apathetic after surgery. Motor improvement and decrease in dopaminergic treatment were similar in both postoperative apathy and non-apathy groups. We found a cluster of significantly greater metabolism in the postoperative apathy group within the cerebellum, brainstem (in particular ventral tegmental area), temporal lobe, insula, amygdala, lentiform nucleus, subgenual anterior cingulate, and inferior frontal gyrus. A metabolic value above 68 could discriminate patients who would develop postoperative apathy with 100% sensitivity and 88.5% specificity. We describe a preoperative metabolic pattern associated with the development of apathy after STN-DBS in PD. This suggests the existence of a predisposition to apathy, which may further be triggered by perioperative drug modifications.
Progressive supranuclear palsy (PSP) is a degenerative disease affecting mainly the brain stem, basal ganglia and cerebellum. Associated cerebrovascular lesions, mainly small cerebral bleeds, are frequently observed in some neurodegenerative diseases such as Alzheimer dementia and rare in others such as frontotemporal lobar degeneration. The present post-mortem study investigates the prevalence and distribution of small cerebral bleeds in PSP brains. Nineteen brains of PSP patients were compared to 12 age-matched controls. The prevalence and distribution of mini-bleeds were investigated on a coronal section of a cerebral hemisphere at the level of the mamillary bodies and on a horizontal section through the pons and cerebellum. In addition, out of these series T2*-weighted gradient-echo 7.0-Tesla magnetic resonance imaging (MRI) of 3 coronal sections of a cerebral hemisphere and of a brain stem and cerebellum was performed in 14 PSP and 11 control brains. Although the total number of mini-bleeds was the same on neuropathological examination of both groups, they prevailed around the dentate nucleus of the cerebellum (p = 0.05) and in the tegmentum pontis (p = 0.05) of the PSP brains. On MRI the small bleeds were also more frequent around the dentate nucleus of the cerebellum (p = 0.02) and in the pons (p = 0.04) of PSP brains. In PSP brains, mini-bleeds only prevail in the regions affected by the neurodegenerative process, similarly to what happens in frontotemporal lobar degeneration. They should be considered as the result of increased angiogenesis and microglial activation, leading to associated disturbances of the blood-brain barrier in the most affected regions of PSP. They are not indicative of cerebrovascular disease.
To detect the presence of hypoxic tissue, which is known to increase the radioresistant phenotype, by its uptake of fluoromisonidazole (18F) (FMISO) using hybrid positron emission tomography/computed tomography (PET/CT) imaging, and to compare it with the glucose-avid tumor tissue imaged with fluorodeoxyglucose (18F) (FDG), in residual postsurgical skull base chordoma scheduled for radiotherapy. Seven patients with incompletely resected skull base chordomas were planned for high-dose radiotherapy (dose ≥70 Gy). All 7 patients underwent FDG and FMISO PET/CT. Images were analyzed qualitatively by visual examination and semiquantitatively by computing the ratio of the maximal standardized uptake value (SUVmax) of the tumor and cerebellum (T/C R), with delineation of lesions on conventional imaging. Of the eight lesion sites imaged with FDG PET/CT, only one was visible, whereas seven of nine lesions were visible on FMISO PET/CT. The median SUVmax in the tumor area was 2.8 g/mL (minimum 2.1; maximum 3.5) for FDG and 0.83 g/mL (minimum 0.3; maximum 1.2) for FMISO. The T/C R values ranged between 0.30 and 0.63 for FDG (median, 0.41) and between 0.75 and 2.20 for FMISO (median,1.59). FMISO T/C R >1 in six lesions suggested the presence of hypoxic tissue. There was no correlation between FMISO and FDG uptake in individual chordomas (r = 0.18, p = 0.7). FMISO PET/CT enables imaging of the hypoxic component in residual chordomas. In the future, it could help to better define boosted volumes for irradiation and to overcome the radioresistance of these lesions. No relationship was founded between hypoxia and glucose metabolism in these tumors after initial surgery.
The potassium channel tetramerization domain-containing protein 7 (KCTD7) was named after the structural homology of its predicted N-terminal broad complex, tramtrack and bric à brac/poxvirus and zinc finger domain with the T1 domain of the Kv potassium channel, but its expression profile and cellular function are still largely unknown. We have recently reported a homozygous nonsense mutation of KCTD7 in patients with a novel form of autosomal recessive progressive myoclonic epilepsy. Here, we show that KCTD7 expression hyperpolarizes the cell membrane and reduces the excitability of transfected neurons in patch clamp experiments. We found the expression of KCTD7 in the hippocampal and Purkinje cells of the murine brain, an expression profile consistent with our patients' phenotype. The effect on the plasma membrane resting potential is possibly mediated by Cullin-3, as we demonstrated direct molecular interaction of KCTD7 with Cullin-3 in co-immunoprecipitation assays. Our data link progressive myoclonic epilepsy to an inherited defect of the neuron plasma membrane's resting potential in the brain.
To understand the substrates of response and nonresponse and to identify potential biomarkers for the selection and follow-up of patients with essential tremor (ET) treated with Gamma Knife (Elekta AB, Stockholm, Sweden) of the ventral intermediate nucleus (GKVIM). To characterize positron emission tomography (PET) changes in the metabolism of glucose and metabolic connectivity in patients with ET treated by GKVIM through observational study. Forty-two patients with right ET were referred to 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET) imaging before and after left GKVIM. Statistical Parametric Mapping T-score map comparisons were performed between pre- and post-GKVIM groups and between clinical responders and nonresponders. Metabolic connectivity was evaluated by the interregional correlation analysis method. After GKVIM, patients with ET exhibited decreased left thalamic metabolism, which was associated with remote metabolic decreases in the right cerebellum, left temporal gyri, and bilateral frontal gyri (P < .05, family-wise error-corrected). Additionally, nonresponders (n = 7) showed metabolic decreases in the right temporo-occipital area (P < .005 corrected for cluster volume) after GKVIM. The metabolism in this area was already reduced in nonresponders before treatment in comparison to that in responders and was predictive of future response (sensitivity: 89%; specificity: 71%). In nonresponder patients, strong connectivity between the left thalamus and right temporo-occipital area was found before GKVIM and was lost after treatment, whereas this connectivity remained weak and stable in responders. These findings could lead to better knowledge of the variability in the metabolic PET profiles among patients with ET, particularly the integration of 18F-FDG PET imaging in the pretherapeutic evaluation of patients with refractory ET candidates for GKVIM.
The objectives were to investigate the diffusional kurtosis imaging (DKI) incorporation into the intravoxel incoherent motion (IVIM) model for measurements of cerebral hypoperfusion in healthy subjects. Eight healthy subjects underwent a hyperventilation challenge with a 4-min diffusion weighted imaging protocol, using 8 b values chosen with the Cramer-Rao Lower Bound optimization approach. Four regions of interest in gray matter (GM) were analyzed with the DKI-IVIM model and the bi-exponential IVIM model, for normoventilation and hyperventilation conditions. A significant reduction in the perfusion fraction (f) and in the product fD* of the perfusion fraction with the pseudodiffusion coefficient (D*) was found with the DKI-IVIM model, during the hyperventilation challenge. In the cerebellum GM, the percentage changes were f: -43.7 ± 40.1, p = 0.011 and fD*: -50.6 ± 32.1, p = 0.011; in thalamus GM, f: -47.7 ± 34.7, p = 0.012 and fD*: -47.2 ± 48.7, p = 0.040. In comparison, using the bi-exponential IVIM model, only a significant decrease in the parameter fD* was observed for the same regions of interest. In frontal-GM and posterior-GM, the reduction in f and fD* did not reach statistical significance, either with DKI-IVIM or the bi-exponential IVIM model. When compared to the bi-exponential IVIM model, the DKI-IVIM model displays a higher sensitivity to detect changes in perfusion induced by the hyperventilation condition.
<i><b>Introduction</b>: Mixed dementia (MixD) refers to a combination of definite Alzheimer's disease (AD) and vascular encephalopathy. The existence of a "pure" type of vascular dementia (VaD) is controversial. There is a need to find magnetic resonance imaging (MRI) characteristics allowing the distinction between VaD and MixD. The present post-mortem 7.0-tesla MRI compares the frequency or severity and the topography of the small cerebrovascular lesions in brains of patients with VaD and with MixD. <b>Material and methods</b>: Based on neuropathological criteria, 14 brains were classified as VaD, 24 as MixD and 11 as controls. Three coronal sections of a cerebral hemisphere and a horizontal section of a cerebellar hemisphere underwent T2 and T2* 7.0-tesla MRI examination. The mean values and topographic distribution of white matter changes (WMCs), lacunar infarcts (LIs), cortical microbleeds (CoMBs) and cortical microinfarcts (CoMIs) were determined and compared between the different groups. <b>Results</b>: Compared to the controls, both VaD and MixD brains had significantly more severe WMCs and increased numbers of CoMBs and CoMIs. Lacunar infarcts predominated only in the VaD cases. On mutual comparison of VaD and MixD brains, CoMBs and CoMIs predominated in the frontal lobe and the cerebellum of VaD, while were mainly present in the occipital lobe of MixD. White matter changes predominated in the temporal lobe of MixD cases. Lacunar infarcts were significantly increased in the corona radiata and putamen of VaD patients. <b>Conclusions</b>: The present post-mortem MRI study shows clear differences in the distribution and the types of cerebrovascular lesions on high-field MRI, confirming that VaD and MixD are different diseases. </i>.
The aim of this study was to demonstrate the feasibility to assess cerebral hypoperfusion with a hyperventilation (HV) challenge protocol using intravoxel incoherent motion (IVIM) magnetic resonance imaging. Magnetic resonance imaging experiments were performed on 10 healthy volunteers at 1.5 T, with a diffusion IVIM magnetic resonance imaging protocol using a set of b-values optimized by Cramer-Rao Lower Bound analysis. Hypoperfusion was induced by an HV maneuver. Measurements were performed in normoventilation and HV conditions. Biexponential curve fitting was used to obtain the perfusion fraction (f), pseudodiffusion coefficient (D*), and the product fD* in gray matter (GM) regions of interest (ROIs). Regional cerebral blood flow in the same ROIs was also assessed with arterial spin labeling. The HV challenge led to a diminution of IVIM perfusion-related parameters, with a decrease of f and fD* in the cerebellum (P = 0.03 for f; P = 0.01 for fD*), thalamus GM (P = 0.09 for f; P = 0.01 for fD*), and lenticular nuclei (P = 0.03 for f; P = 0.02 for fD*). Mean GM cerebral blood flow (in mL/100 g tissue/min) measured with arterial spin labeling averaged over all ROIs also decreased (normoventilation: 42.7 ± 4.1 vs HV: 33.2 ± 2.2, P = 0.004) during the HV challenge. The optimized IVIM protocol proposed in the current study allows for measurements of cerebral hypoperfusion that might be of great interest for pathologies diagnosis such as ischemic stroke.
Essential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard surgical stereotactic procedures (deep brain stimulation, thalamotomy) or minimally invasive high-intensity focused ultrasound (HIFU) or stereotactic radiosurgical thalamotomy (SRS-T). Resting-state fMRI (rs-fMRI) is a non-invasive imaging method acquired in absence of a task. We examined whether rs-fMRI correlates with tremor score on the treated hand (TSTH) improvement 1 year after SRS-T. We included 17 consecutive patients treated with left unilateral SRS-T in Marseille, France. Tremor score evaluation and rs-fMRI were acquired at baseline and 1 year after SRS-T. Resting-state data (34 scans) were analyzed without a priori hypothesis, in Lausanne, Switzerland. Based on degree of improvement in TSTH, to consider SRS-T at least as effective as medication, we separated two groups: 1, ≤ 50% (n = 6, 35.3%); 2, > 50% (n = 11, 64.7%). They did not differ statistically by age (p = 0.86), duration of symptoms (p = 0.41), or lesion volume at 1 year (p = 0.06). We report TSTH improvement correlated with interconnectivity strength between salience network with the left claustrum and putamen, as well as between bilateral motor cortices, frontal eye fields and left cerebellum lobule VI with right visual association area (the former also with lesion volume). Longitudinal changes showed additional associations in interconnectivity strength between right dorsal attention network with ventro-lateral prefrontal cortex and a reminiscent salience network with fusiform gyrus. Brain connectivity measured by resting-state fMRI relates to clinical response after SRS-T. Relevant networks are visual, motor, and attention. Interconnectivity between visual and motor areas is a novel finding, revealing implication in movement sensory guidance.
Essential tremor (ET) represents the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic procedures (deep brain stimulation or radiofrequency thalamotomy) or alternatively minimally invasive high-focused ultrasound or radiosurgery. All aim at same target, thalamic ventro-intermediate nucleus (Vim). The study included a cohort of 17 consecutive patients, with ET, treated only with left unilateral stereotactic radiosurgical thalamotomy (SRS-T) between September 2014 and August 2015. The mean time to tremor improvement was 3.32 months (SD 2.7, 0.5-10). Neuroimaging data were collected at baseline (n = 17). Standard tremor scores, including activities of daily living (ADL) and tremor score on treated hand (TSTH), were completed pretherapeutically and 1 year later. We further correlate these scores with baseline inter-connectivity in twenty major large-scale brain networks. We report as predictive three networks, with the interconnected statistically significant clusters: primary motor cortex interconnected with inferior olivary nucleus, bilateral thalamus interconnected with motor cerebellum lobule V (ADL), and anterior default-mode network interconnected with Brodmann area 10 (TSTH). For all, more positive pretherapeutic interconnectivity correlated with higher drop in points on the respective scores. Age, disease duration, or time-to-response after SRS-T were not statistically correlated with pretherapeutic brain connectivity measures (P > .05). The same applied to pretherapeutic tremor scores, after using the same methodology described above. Our findings have clinical implications for predicting clinical response after SRS-T. Here, using pretherapeutic magnetic resonance imaging and data processing without prior hypothesis, we show that pretherapeutic network(s) interconnectivity strength predicts tremor arrest in drug-naïve ET, following stereotactic radiosurgical thalamotomy.