Simone Marziali

Temporal window of metabolic brain vulnerability to concussion: A pilot 1H-magnetic resonance spectroscopic study in concussed athletes - Part III

OBJECTIVE In the present study, the occurrence of the temporal window of brain vulnerability was evaluated in concussed athletes by measuring N-acetylaspartate (NAA) using proton magnetic resonance (H-MR) spectroscopy. METHODS Thirteen nonprofessional athletes who had a sport-related concussive head injury were examined for NAA determination by means of H-MR spectroscopy at 3, 15, and 30 days postinjury. All athletes but three suspended their physical activity. Those who continued their training had a second concussive event and underwent further examination at 45 days from the initial injury. The single case of one professional boxer, who was studied before the match and 4, 7, 15, and 30 days after a knockout, is also presented. Before each magnetic resonance examination, patients were asked for symptoms of mild traumatic brain injury, including physical, cognitive, emotional, and sleep disturbances. Data for H-MR spectroscopy recorded in five normal, age-matched, control volunteers, who were previously screened to exclude previous head injuries, were used for comparison. Semiquantitative analysis of NAA relative to creatine (Cr)- and choline (Cho)-containing compounds was performed from proton spectra obtained with a 3-T magnetic resonance system. RESULTS Regarding the values of the NAA-to-Cr ratio (2.21 +/- 0.11) recorded in control patients, singly concussed athletes, at 3 days after the concussion, showed a decrease of 18.5% (1.80 +/- 0.04; P < 0.001). Only a modest 3% recovery was observed at 15 days (1.88 +/- 0.1; P < 0.001); at 30 days postinjury, the NAA-to-Cr ratio was 2.15 +/- 0.1, revealing full metabolic recovery with values not significantly different from those of control patients. These patients declared complete resolution of symptoms at the time of the 3-day study. The three patients who had a second concussive injury before the 15-day study showed an identical decrease of the NAA-to-Cr ratio at 3 days (1.78 +/- 0.08); however, at 15 days after the second injury, a further diminution of the NAA-to-Cr ratio occurred (1.72 +/- 0.07; P < 0.05 with respect to singly concussed athletes). At 30 days, the NAA-to-Cr ratio was 1.82 +/- 0.1, and at 45 days postinjury, the NAA-to-Cr ratio showed complete recovery (2.07 +/- 0.1; not significant with respect to control patients). This group of patients declared a complete resolution of symptoms at the time of the 30-day study. CONCLUSION Results of this pilot study carried out in a cohort of singly and doubly concussed athletes, examined by H-MR spectroscopy for their NAA cerebral content at different time points after concussive events, demonstrate that also in humans, concussion opens a temporal window of brain metabolic imbalance, the closure of which does not coincide with resolution of clinical symptoms. The recovery of brain metabolism is not linearly related to time. A second concussive event prolonged the time of NAA normalization by 15 days. Although needing confirmation in a larger group of patients, these results show that NAA measurement by H-MR spectroscopy is a valid tool in assessing the full cerebral metabolic recovery after concussion, thereby suggesting its use in helping to decide when to allow athletes to return to play after a mild traumatic brain injury.

Proposed chronic cerebrospinal venous insufficiency criteria do not predict multiple sclerosis risk or severity.

It is still unclear whether chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS), because substantial methodological differences have been claimed by Zamboni to account for the lack of results of other groups. Furthermore, the potential role of venous malformations in influencing MS severity has not been fully explored. This information is particularly relevant, because uncontrolled surgical procedures are increasingly offered to MS patients to treat their venous stenoses.

Decrease in N-Acetylaspartate Following Concussion May Be Coupled to Decrease in Creatine.

Objectives:To assess the time course changes in N-acetylaspartate (NAA) and creatine (Cr) levels in the brain of athletes who suffered a sport-related concussion. Participants:Eleven nonconsecutive athletes with concussive head injury and 11 sex- and age-matched control volunteers Main outcome measures:At 3, 15, 30, and 45 days postinjury, athletes were examined by proton magnetic resonance spectroscopy for the determination of NAA, Cr, and choline (Cho) levels. Proton magnetic resonance spectroscopic data recorded for the control group were used for comparison. Results:Compared with controls (2.18 ± 0.19), athletes showed an increase in the NAA/Cr ratio at 3 (2.71 ± 0.16; P < .01) and 15 (2.54 ± 0.21; P < .01) days postconcussion, followed by a decrease and subsequent normalization at 30 (1.95 ± 0.16, P < .05) and 45 (2.17 ± 0.20; P < .05) days postconcussion. The NAA/Cho ratio decreased at 3, 15, and 30 days postinjury (P < .01 compared with controls), with no differences observed in controls at 45 days postconcussion. Compared with controls, significant increase in the Cho/Cr ratio after 3 (+33%, P < .01) and 15 (+31.5%, P < .01) days postinjury was observed whereas no differences were recorded at 30 and 45 days postinjury. Conclusions:This cohort of athletes indicates that concussion may cause concomitant decrease in cerebral NAA and Cr levels. This provokes longer time for normalization of metabolism, as well as longer time for resolution of concussion-associated clinical symptoms.

Differences between Proximal versus Distal Intraorbital Optic Nerve Diffusion Tensor Magnetic Resonance Imaging Properties in Glaucoma Patients

PURPOSE To analyze in vivo the diffusion tensor magnetic resonance imaging (DT-MRI) properties of the intraorbital optic nerve at two different levels: Proximal to the optic nerve head (ONH) and distal to the ONH at the level of the orbital apex in glaucoma patients. METHODS Twenty-four patients with primary open-angle glaucoma were examined. The categorization into early and severe glaucoma was performed by Hodapps classification. Fifteen healthy individuals served as controls. DT-MRI was performed with a 3T-MR unit. RESULTS At early stage mean diffusivity (MD) values were higher at the proximal site with respect to the distal site. On the contrary, a decrease in fractional anisotropy (FA) was observed only relative to patient stage, independent of optic nerve site. Moreover, at early disease stage an increase in overall diffusivities, was evident at the proximal site, whereas at the distal site a decrease of the largest diffusivity and an increase in both the intermediate and smallest diffusivities were observed. FA and MD measured at the proximal site, had, respectively, the highest sensitivity and specificity in discriminating between healthy and glaucomatous eyes. CONCLUSIONS Our study represents the first attempt to evaluate in vivo fiber integrity changes along the optic nerve with DT-MRI. Optic nerve degeneration appears to be a process that affects differently the proximal and the distal segments of the optic nerve. The complementary high sensitivity of FA with the high specificity of MD at the proximal site may provide reliable indexes for the identification of glaucomatous patients at early stages.

Floating carotid thrombus treated by intravenous heparin and endarterectomy

Among different subtypes of ischemic stroke, atherosclerotic stroke carries the greatest risk (30%) of worsening and recurrence during the acute phase of hospitalization with a 7.9% risk ≤ 30 days. Causes of this high risk include plaque rupture leading to thrombus formation, thrombus propagation with consequent vessel occlusion, and distal embolism. In this context, emergent endarterectomy or anticoagulation, followed by deferred endarterectomy, are both controversial. We report a patient with an ischemic stroke caused by thromboembolism from an ulcerated plaque with floating thrombus of the internal carotid artery (ICA). A controversial use of heparin is discussed.

The Importance of Restriction from Physical Activity in the Metabolic Recovery of Concussed Brain

Brain concussion is unquestionably the most common form of traumatic brain injury (TBI) worldwide (Bruns & Hauser, 2003; Tagliaferri et al., 2006). In European countries, approximately 235 individual/100,000 people are admitted annually to the hospital following TBI, 80% of which receive a diagnosis of mild TBI (mTBI). (van der Naalt, 2001; Vos et al., 2002). It has been calculated that the ratio in the occurrence of mTBI to severe TBI (sTBI) is approximately 22 to 1, with mTBI accounting for at least 75% of patients who survive after TBI each year (Tagliaferri et al., 2006). These percentages are very similar to those recorded in the United States where it is estimated that approximately 1.5 – 8 million people per year suffer from TBI and, among those requiring hospitalization, a proportion ranging from 75% to 90% are classified as “mildly” injured or “concussed” (Bruns & Hauser, 2003). These wide ranges of annual incidence are probably due to the fact that an unknown proportion of mTBI victims do not seek any medical attention (McCrea et al., 2004) (HEADS UP) but it might also be due to the fact that there is still confusion and inconsistency among researchers and organizations in defining and understanding this type of trauma. (Cantu & Voy, 1995; Cantu, 1998, 2007). The above reported numbers give the evidence that albeit the incidence of mTBI is tremendously high, the mortality caused by this type of trauma appears to be rather low (610 per 100,000/year). To reinforce this concept it has been reported that only 0.2% of all

Acute disseminated encephalomyelitis following Campylobacter jejuni gastroenteritis: Case report and review of the literature.

We describe a case of a 25-year-old male with a diagnosis of acute disseminated encephalomyelitis (ADEM) following infection with Campylobacter jejuni, which is implicated in various human pathologies regarding the central nervous system (CNS) with acute course like Guillain-Barré syndrome (GBS), Miller-Fisher syndrome (MFS), Bickerstaff’s brainstem encephalitis (BEE), acute transverse myelitis (ATM) as well as ADEM. These conditions are caused by cross-reactivity between Campylobacter’s epitopes and cells of the CNS that causes an immunomediated inflammatory demyelination of the CNS. In the acute phase, magnetic resonance (MR) can detect pathologic signal intensity at the CNS with areas of pathologic contrast enhancement at cortical and spinal white matter that normalize over time or can be stable. These findings can be associated with edema in parts of the CNS. The lesions typically appear at different times during the disease course and also can have a different evolution. Our purpose therefore was to describe the clinical course and MR findings of this case and perform a critical review of the literature.

Cerebral cavernous malformations associated to meningioma: High penetrance in a novel family mutated in the PDCD10 gene.

Multiple familial meningiomas occur in rare genetic syndromes, particularly neurofibromatosis type 2. The association of meningiomas and cerebral cavernous malformations (CCMs) has been reported in few patients in the medical literature. The purpose of our study is to corroborate a preferential association of CCMs and multiple meningiomas in subjects harbouring mutations in the PDCD10 gene (also known as CCM3). Three members of an Italian family affected by seizures underwent conventional brain Magnetic Resonance Imaging (MRI) with gadolinium contrast agent including gradient echo (GRE) imaging. The three CCM-causative genes were sequenced by Sanger method. Literature data reporting patients with coexistence of CCMs and meningiomas were reviewed. MRI demonstrated dural-based meningioma-like lesions associated to multiple parenchymal CCMs in all affected individuals. A disease-causative mutation in the PDCD10 gene (p.Gln112PhefsX13) was identified. Based on neuroradiological and molecular data as well as on literature review, we outline a consistent association between PDCD10 mutations and a syndrome of CCMs with multiple meningiomas. This condition should be considered in the differential diagnosis of multiple/familial meningioma syndromes. In case of multiple/familial meningioma the use of appropriate MRI technique may include GRE and/or susceptibility-weighted imaging (SWI) to rule out CCM. By contrast, proper post-gadolinium scans may aid defining dural lesions in CCM patients and are indicated in PDCD10-mutated individuals.

Brain MR diffusion tensor imaging in Kennedy's disease

Introduction Kennedy’s disease (KD) is a progressive degenerative disorder affecting lower motor neurons. We investigated the correlation between disease severity and whole brain white matter microstructure, including upper motor neuron tracts, by using diffusion-tensor imaging (DTI) in eight patients with KD in whom disease severity was evaluated using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS). Methods From DTI acquisitions we obtained maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1) and radial diffusivities (L2, L3). We then employed tract-based spatial statistics (TBSS) to investigate within-patient correlations of DTI invariants with ALSFRS and disease duration (DD). Results We found a significant correlation between low ALSFRS and 1) low FA values in association commissural and projection fibers, and 2) high L3 values in commissural tracts and fronto-parietal white matter. Additionally, we found a significant association between longer DD and 1) low FA in the genu and body of corpus callosum, association fibers and midbrain and 2) high L1 in projection and association tracts. Conclusions The associations between clinical variables and white matter microstructural changes in areas thought to be spared by the disease process support the hypothesis of a multisystem involvement in the complex pathogenic mechanisms responsible for the clinical disability of these patients.

Difficulty diagnosing chronic cryptococcal meningitis in idiopathic CD4+ lymphocytopenia

A 64-year-old man with idiopathic CD4+ lymphocytopenia developed cognitive impairment and gait ataxia with isolated obstructive hydrocephalus, which was fatal. Cerebrospinal fluid showed mild pleocytosis, but the etiology was not revealed by extensive analysis. At autopsy, inflammatory cells, CD8+ lymphocytes and abundant macrophages but not CD4+ lymphocytes were infiltrating the meninges at the base of the brain. Electron microscopy demonstrated that inflammation was caused by Cryptococcus neoformans, which was localized exclusively within macrophages, where it grew with budding. Our study suggests that, in idiopathic CD4+ lymphocytopenia, macrophages can efficiently phagocytize but inefficiently digest C. neoformans, thus representing a vehicle of chronic intracellular infection.