SPECT analysis and language profile in Greek speaking patients with subtypes of frontotemporal dementia.

OBJECTIVE: We aimed to examine if single photon emission computed tomography (SPECT) can discriminate between variants of frontotemporal dementia (FTD). As a secondary investigation we identify and establish the linguistic differences between those variants. MATERIALS AND METHODS: Nine patients with semantic variant primary progressive aphasia (svPPA), 8 with non-fluent variant primary progressive aphasia (nfvPPA) and 17 with behavioral variant of frontotemporal dementia (bvFTD) were compared on Addenbrooke's cognitive examination-revised (ACE-R), auditory comprehension, oral expression and verbal fluency. All patients were also compared with healthy controls. Patients were evaluated using technetium-99m-hexamethylproyleneamine oxime (99mTc-HMPAO) brain SPECT as a measure of regional cerebral flow. RESULTS: Significant group differences between all patients and controls were found for ACE-R, auditory comprehension and oral expression. Semantic variant primary progressive aphasia patients performed higher in letter compared to category fluency with significant deficits in auditory comprehension and oral expression. Non-fluent variant primary progressive aphasia patients showed significant deficits in auditory comprehension but not oral expression while performed lightly worse in letter fluency compared to category. Behavioral variant of frontotemporal dementia patients showed deficits in auditory comprehension and oral expression and performed similar in category and letter fluency. Single photon emission computed tomography analysis revealed left frontotemporal hypoperfusion extending to the right frontotemporal region in svPPA patients. Non-fluent variant primary progressive aphasia patients presented left frontotemporal hypoperfusion with participation of the left parietal and right frontotemporal regions. Behavioral variant of frontotemporal dementia patients showed bilateral frontotemporal hypoperfusion compared to parietal and visual cortices. CONCLUSION: Our findings suggest that SPECT may assist in the discrimination of the FTD variants. We also confirmed that bvFTD patients share similar language deficits with svPPA patients.

Cognitive Reserve Hypothesis in Frontotemporal Dementia: Evidence from a Brain SPECT Study in a Series of Greek Frontotemporal Dementia Patients.

BACKGROUND AND OBJECTIVE: Cognitive reserve (CR) mediates the clinical expression of brain pathology in Alzheimer's disease, while there are much less relevant data in frontotemporal dementia (FTD). In the present study we examined whether CR, measured using the Cognitive Reserve Index (CRI), correlated with regional cerebral blood flow (rCBF) in Greek FTD patients. METHODS: Eighty FTD patients, i.e., 47 with behavioral variant FTD (bvFTD) and 33 with primary progressive aphasia (PPA), were enrolled into this study. CR was assessed using the CRI questionnaire, which provides a total score (CRI) and 3 subscores, i.e., CRI-education, CRI-working activity, and CRI-leisure time. The FTD-Clinical Dementia Rating Scale was used to assess the severity of dementia and a brain SPECT study was performed to measure rCBF. Finally, multiple regression analyses were conducted to explore correlations between CR indices and frontotemporal rCBF. RESULTS: In both the bvFTD and the PPA groups, higher scores in the CRI, CRI-education, and CRI-leisure time correlated with lower rCBF in the bilateral frontal and left temporal cortex, respectively, controlling for age, sex, time since symptom onset, and disease severity. CONCLUSION: In the present study, lifetime participation in leisure time activities was found to mitigate the burden of disease in bvFTD and PPA patients. Moreover, FTD patients with a higher educational attainment were able to cope better with greater brain damage. Determination of the most suitable activities to build an adequate level of CR is crucial for dementia prevention.

Charcot-Marie-Tooth Disease 1X Simulating Paraparetic Guillain-Barre Syndrome.

X-linked Charcot-Marie-Tooth disease (CMT 1X) is the second most common form of inherited demyelinating neuropathy. It is established that patients suffering from CMT 1X can have episodes of hemiparesis, paraparesis, quadriparesis, ataxia, aphasia, and dysarthria, which can be fully reversible, and 'trigger' factors for these episodes are usually febrile illness, high altitudes, hyperventilation, and physical activity. We describe a 22-year-old patient with a history of viral infection and sleep deprivation who presented to our department because of acute difficulty in walking and neurophysiological findings suggesting Guillain-Barre syndrome. The patient's phenotype was compatible with CMT disease and within hours he showed remarkable improvement of his muscle strength without receiving any medical treatment. Any other metabolic, infectious, vasculitic, hematological, paraneoplastic, or infiltrative cause of polyneuropathy was excluded with laboratory work-up. Diagnosis of CMT 1X was confirmed with repeated neurophysiological study and genetic testing of his and his mother's blood, demonstrating the Arg75Trp [CGG to TGG,(R75W)] mutation on exon2 of gap junction protein beta 1. CMT 1X should be considered in patients with a phenotype compatible with the disease, rapid improvement of their clinical manifestations, and neurophysiological findings consistent with a hereditary, demyelinating neuropathy.

Frontotemporal Lobar Degeneration-Modified Clinical Dementia Rating (FTLD-CDR) Scale and Frontotemporal Dementia Rating Scale (FRS) Correlation With Regional Brain Perfusion in a Series of FTLD Patients.

Severity assessment scales for frontotemporal lobar degeneration (FTLD) have been recently introduced. In the present study, the authors examined whether the FTLD-modified Clinical Dementia Rating (FTLD-CDR) scale and the Frontotemporal Dementia Rating Scale (FRS) correlated with regional brain perfusion in Greek FTLD patients. A total of 47 behavioral variant frontotemporal dementia (bvFTD) patients and 33 primary progressive aphasia (PPA) patients were assessed for demographic data, cognitive reserve (CR), and severity of dementia and underwent brain single-photon emission computed tomography. Both scales were valid in the bvFTD group, predicting frontal lobe perfusion. In the PPA group, both scales were found to predict temporal hypoperfusion only after accounting for CR, which could imply a potential role for reserve in PPA patients.

Nogo receptor complex expression dynamics in the inflammatory foci of central nervous system experimental autoimmune demyelination.

BACKGROUND: Nogo-A and its putative receptor NgR are considered to be among the inhibitors of axonal regeneration in the CNS. However, few studies so far have addressed the issue of local NgR complex multilateral localization within inflammation in an MS mouse model of autoimmune demyelination. METHODS: Chronic experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. Analyses were performed on acute (days 18-22) and chronic (day 50) time points and compared to controls. The temporal and spatial expression of the Nogo receptor complex (NgR and coreceptors) was studied at the spinal cord using epifluorescent and confocal microscopy or real-time PCR. Data are expressed as cells/mm2, as mean % ± SEM, or as arbitrary units of integrated density. RESULTS: Animals developed a moderate to severe EAE without mortality, followed by a progressive, chronic clinical course. NgR complex spatial expression varied during the main time points of EAE. NgR with coreceptors LINGO-1 and TROY was increased in the spinal cord in the acute phase whereas LINGO-1 and p75 signal seemed to be dominant in the chronic phase, respectively. NgR was detected on gray matter NeuN+ neurons of the spinal cord, within the white matter inflammatory foci (14.2 ± 4.3 % NgR+ inflammatory cells), and found to be colocalized with GAP-43+ axonal growth cones while no ß-TubIII+, SMI-32+, or APP+ axons were found as NgR+. Among the NgR+ inflammatory cells, 75.6 ± 9.0 % were microglial/macrophages (lectin+), 49.6 ± 14.2 % expressed CD68 (phagocytic ED1+ cells), and no cells were Mac-3+. Of these macrophages/monocytes, only Arginase-1+/NgR+ but not iNOS+/NgR+ were present in lesions both in acute and chronic phases. CONCLUSIONS: Our data describe in detail the expression of the Nogo receptor complex within the autoimmune inflammatory foci and suggest a possible immune action for NgR apart from the established inhibitory one on axonal growth. Its expression by inflammatory macrophages/monocytes could signify a possible role of these cells on axonal guidance and clearance of the lesioned area during inflammatory demyelination.

Adaptation of the Cognitive Reserve Index Questionnaire (CRIq) for the Greek population.

Cognitive reserve (CR) is thought to reflect the cumulative brain potential derived from various cognitively demanding activities throughout the entire life. It seems to mediate both one's cognitive performance and clinical expression of different brain pathologies, such as Alzheimer's disease. Many researchers have tried to assess CR by using proxies, such as educational and occupational level, participation in leisure time activities and intelligence, alone or in various combinations. Recently, a new tool for measuring CR status was constructed, the Cognitive Reserve Index questionnaire (CRIq), comprising of all known CR proxies. CRIq also takes into account the amount of time spent during each of these activities, thus capturing the core idea behind CR theory: its active day to day formulation during all age stages. Aim of the present study was to adapt CRIq for the Greek population. The questionnaire was administered to 591 participants (age range 18-89) stratified in three age groups (young adults, middle-aged, elderly). The middle-aged group showed higher total CRI as well as CRI-Education, CRI-WorkingActivity and CRI-LeisureTime scores compared to both other groups, reflecting more years of engagement in all activities. Gender also influenced CRI scores, with men scoring higher than women, again resulting from historical and social perspectives. Overall, the CRIq showed satisfactory internal consistency, was easy to administer and its adaptation process provided solid and interpretable results. The Greek version of CRIq enriches existing dementia research methodology and allows for valid results in an ever growing field.

Subcutaneous Transplantation of Neural Precursor Cells in Experimental Autoimmune Encephalomyelitis Reduces Chemotactic Signals in the Central Nervous System.

UNLABELLED: Neural precursor cell (NPC) transplantation has been proposed as a therapy for multiple sclerosis (MS) and other degenerative disorders of the central nervous system (CNS). NPCs are suggested to exert immune modulation when they are transplanted in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Herein, we explore whether the effect of NPC transplantation on the clinical course and the pathological features of EAE is combined with the modulation of chemokines levels expressed in the inflamed CNS. NPCs were isolated from brains of neonatal C57/Bl6 mice and were subcutaneously administered in female mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Clinical signs of the disease and transcript analysis of the CNS in the acute phase were performed. In addition, the presence of inflammatory components in the spinal cord was evaluated and ex vivo proliferation of lymphocytes was measured. NPC recipients exhibited ameliorated clinical outcome and less pronounced pathological features in their spinal cord. Downregulation of chemokine mRNA levels throughout the CNS was correlated with diminished Mac-3-, CD3-, and CD4-positive cells and reduced expression levels of antigen-presenting molecules in the spinal cord. Moreover, NPC transplantation resulted in lymphocyte-related, although not splenocyte-related, peripheral immunosuppression. We conclude that NPCs ameliorated EAE potentially by modulating the levels of chemokines expressed in the inflamed CNS, thus resulting in the impaired recruitment of immune cells. These findings further contribute to the better understanding of NPCs' immunomodulatory properties in neuroinflammatory disorders, and may lead to faster translation into potential clinical use. SIGNIFICANCE: Endogenous neural precursor cells of the central nervous system are able to migrate and differentiate toward mature cells to repair an injury. There is increasing evidence that autologous transplantation of these cells in experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis, may have a beneficial effect on the disease process. Several mechanisms have been proposed-among them, the potentiation of endogenous precursor cell differentiation of the central nervous system and the modulation of demyelinating and neurodegenerative immune-mediated processes. This article provides evidence of interference in immune signaling within the central nervous system as a potential mechanism underlying the immunomodulatory properties of transplanted neural precursor cells.

Muscular dystrophy in a patient with multiple sclerosis. Another "double-trouble"?

Facioscapulohumeral muscular dystrophy (FSHD) is considered a relatively common muscular dystrophy affecting approximately 1:15,000 individuals in the general population. Single case reports have described the rare co-occurrence of FSHD with other hereditary neuromuscular disorders, leading to atypical phenotypes. We report herein the case of a 26-year-old woman with genetically proven FSHD, who additionally developed otherwise typical multiple sclerosis (MS). Although there is no direct relationship between FSHD and MS, they might, nevertheless, share some common pathophysiological mechanisms, as recent research suggests. In particular, we comment on the potential, but not yet proven, role of immunological factors in the pathogenesis of FSHD.

Internal carotid artery floating thrombus in relapsing polychondritis.

Relapsing polychondritis is a rare autoimmune disease characterized by inflammation of cartilaginous tissues. It may be associated with systemic and cerebral vasculitis and exceptionally with ischemic stroke. Brain infarction associated with internal carotid artery thrombus, in a setting of relapsing polychondritis, has never been reported. We present a 52-year-old man without any known risk factors for stroke, treated with prednisone and azathioprine for relapsing polychondritis, who presented a minor left hemisphere stroke. Ultrasound of the neck vessels revealed an isoechogenic thrombus in the left internal carotid artery superimposed on a smooth moderately stenosing isoechogenic atheroma of the carotid bulb. The patient was treated with high-dose tinzaparin and was followed with serial ultrasound. After 16 days, the thrombus demonstrated a hypoechogenic core surrounded by a hyperechogenic rim and the following day it resolved completely. Thrombus formation on a small unruptured plaque may reflect involvement by relapsing polychondritis of the intimal proteoglycans that hold a role in the development of atheromatosis.

Behavioral disturbances differentiate frontotemporal lobar degeneration subtypes and Alzheimer's disease: evidence from the Frontal Behavioral Inventory.

BACKGROUND: Behavioral assessment is useful for the diagnosis of frontotemporal lobar degeneration (FTLD). We explored the ability of the Frontal Behavioral Inventory (FBI) to discriminate between patients with distinct subtypes of FTLD and patients with Alzheimer's disease (AD), as well as the influence of demographic variables on FBI scores. METHODS: The FBI was administered to the caregivers of 87 patients diagnosed with FTLD [64 behavioral variant FTLD, 19 aphasic variant FTLD (primary progressive aphasia), and 4 motor/extrapyramidal variant (corticobasal syndrome)] and 30 patients with AD. Patients with AD were older than patients with FTLD. The two groups did not differ with respect to duration of illness, level of education, or sex ratio. RESULTS: Age significantly predicted disinhibited positive behaviors, such as perseverations and irritability, whereas education did not contribute to FBI ratings. Classification accuracy for the discrimination of AD and mixed FTLD groups was 81%. Moreover, 88.3% and 83.7% accuracy was achieved for the discrimination of AD and behavioral variant FTLD, and AD and primary progressive aphasia groups, respectively. The Total Negative subscale of the FBI, which summarizes the presence of deficit (negative) behaviors, was the best discriminator. A cut-off score of 17 provided 83% sensitivity and 98% specificity in distinguishing between FTLD and AD patients. CONCLUSIONS: The FBI is a sensitive and specific tool for the differential diagnosis of FTLD from AD. The optimal cut-off point for the detection of FTLD patients was lower than that initially proposed.

Aortic graft infection as a cause of multiple brain infarcts.

Brain embolism of cardiac origin is common in clinical practice. However, embolic brain infarcts due to aortic graft infection are very rare. We present a case of a 53-year-old woman with multiple brain infarcts, following an infection of ascending aortic graft. She was presented with fever and acute onset neurological deficit, and she had a previous history of replacement of ascending aorta with a prosthetic graft, because of aortic aneurysm 2 years before her admission. The patient had positive blood cultures and echocardiographic evidence of vegetation in the graft aortic joint, nearby the aortic valves. Despite the severe clinical condition and the poor prognosis, because of the coexistence of cardioembolism and aortic graft infection, our patient had a good outcome with conservative treatment and she will be considered for surgical graft replacement after her full recovery.

Parry-Romberg Syndrome Associated with Localized Scleroderma.

Parry-Romberg syndrome is a rare neurocutaneous disorder of unknown origin. It is characterized by progressive facial hemiatrophy and frequently overlaps with a condition known as linear scleroderma 'en coup de sabre'. Neurological involvement is frequently described in these patients, including migraine, facial pain and epilepsy, which represent the commonest neurological conditions, sometimes associated with brain abnormalities ipsilaterally to the skin lesions. We present a case of Parry-Romberg syndrome with neurological involvement in a patient with diagnosed localized scleroderma (morphea).