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1.
J Comput Assist Tomogr ; 44(1): 59-64, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939883

RESUMO

PURPOSE: The aim of this study was to investigate correlations between clinical symptoms, cerebrospinal fluid flow metrics, hydrocephalus index, small-vessel disease, and white matter (WM) changes in normal pressure hydrocephalus (NPH). METHODS: Aquaductal stroke volumes (ASVs), Z Evans index, Fazekas grading (FG), and diffusion tensor imaging measurements from WM bundles of 37 patients with NPH were retrospectively evaluated. Mann-Whitney U test between clinical symptoms and other variables and Spearman ρ correlations for relationships between variables and Kruskal-Wallis to correlate FG with nonclinical variables were used. RESULTS: Patients with NPH had increased ASV (median 53 µL). No correlation was found between Z Evans index and ASV. Three groups of patients with dementia or ataxia or incontinence had increased ASV values than their counterparts without symptoms (55 vs 48.5 µL, 75 vs 47 µL, 64 vs 49.5 µL, respectively). Patients having 2 common symptoms of dementia and ataxia and patients having all 3 symptoms of dementia, ataxia, and incontinence were compared with ASV values of 63.5 versus 78 µL, respectively. Patients with FG 1 had median ASV values of 45 µL; FG 2, 82.5 µL; and FG 3, 59 µL. Patients with dementia had significantly higher apparent diffusion coefficient (ADC) values of corona radiata (CR) on both sides. There were no significant WM changes in patients with ataxia and incontinence. The Z Evans index was positively correlated with ADC values of CR on both sides and genu of corpus callosum. Fazekas grading was found positively correlated with ADC and negatively correlated with FA values of CR. CONCLUSIONS: Patients with NPH, regardless of stages of the diseases, have increased ASV values and could benefit from shunting. Decreasing ASV values of patients with FG 3 comparing with those with FG 2 support the hypothesis of decreasing compliance of brain with aging and increasing severity of small-vessel disease.


Assuntos
Líquido Cefalorraquidiano/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Substância Branca/diagnóstico por imagem , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Masculino , Estudos Retrospectivos
2.
Psychogeriatrics ; 19(6): 527-538, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30916850

RESUMO

AIM: Alzheimer's disease (AD) pathology is highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), and the presence of AD pathology may involve regional cerebral blood flow (rCBF). In this study, we examined the relationship between rCBF and AD-related biomarkers in the cerebrospinal fluid of iNPH patients. METHODS: Patients with iNPH (n = 39) were classified into groups with (iNPH/AD+) (n=15) and without (iNPH/AD-) (n=24) high biomarker probability of AD (i.e. combined low amyloid ß 42 and high total tau in the cerebrospinal fluid). rCBF was quantified in 17 regions of interest by N-isopropyl-p-[123 I]iodoamphetamine single-photon emission computed tomography with the autoradiography method. We compared rCBF between the iNPH/AD- and iNPH/AD+ groups at baseline using a t-test and then compared changes in rCBF after shunt surgery between the groups using a paired t-test and two-way repeated measures ANOVA. RESULTS: At baseline, there were no significant differences in rCBF between the groups in most regions apart from the putamen. After shunt surgery, a significant increase in rCBF in the putamen, amygdala, hippocampus, and parahippocampal gyrus was observed in iNPH/AD- patients. In iNPH/AD+ patients, no significant improvement in rCBF was observed in any region. In repeated measures analysis of variance, a significant group × shunt interaction was observed in the parietal lobe, frontal lobe, posterior cingulate cortex, precuneus, lateral temporal lobe, amygdala, hippocampus, parahippocampal gyrus, and putamen. CONCLUSIONS: Improvement in rCBF after shunt surgery in iNPH/AD+ patients may be poorer than that in iNPH AD- patients.


Assuntos
Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Circulação Cerebrovascular , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/metabolismo , Feminino , Humanos , Hidrocefalia de Pressão Normal/sangue , Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Proteínas tau/metabolismo
3.
Neuroradiology ; 61(6): 659-666, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915496

RESUMO

PURPOSE: To identify if specific findings on magnetic resonance imaging (MRI) cerebrospinal fluid (CSF) flow studies can be utilised to identify which patients with idiopathic normal pressure hydrocephalus (iNPH) will have improved gait following a CSF tap test (TT). METHODS: Prospective study of patients undergoing a CSF TT for iNPH. Functional gait was assessed using the timed up and go (TUG) test before and after the CSF TT. MRI CSF flow studies accompanied the CSF TT. The minimum clinically important difference for the TUG (3.63 s) was used as a cutoff value to categorise patients as responders to the CSF TT. RESULTS: Fifty-three patients underwent CSF TT and MRI CSF flow studies. Significant differences were identified between groups for (non-responder vs responder) superior sagittal sinus flow (47.10% vs 40.41%), sagittal sinus stroke volume (274 vs 176.5 µl), sagittal sinus to arterial stroke volume ratio (0.203 vs 0.164), sagittal sinus area (42.2 mm2 vs 36.2 mm2) and circumference (27.7 mm vs 24.95 mm). No differences were present for aqueduct stroke volume, arterial stroke volume or aqueduct net flow. CONCLUSION: A link between gait improvement resulting from CSF drainage and sagittal sinus measurements indicates that the sagittal sinus may play a role in the manifestation of symptoms in iNPH. This may have implications for the diagnosis of iNPH and potentially inform clinical decision making regarding surgical intervention.


Assuntos
Derivações do Líquido Cefalorraquidiano , Transtornos Neurológicos da Marcha/líquido cefalorraquidiano , Transtornos Neurológicos da Marcha/terapia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/terapia , Imagem por Ressonância Magnética/métodos , Seio Sagital Superior/diagnóstico por imagem , Idoso , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Hidrocefalia de Pressão Normal/fisiopatologia , Masculino , Estudos Prospectivos , Resultado do Tratamento
4.
Arch Phys Med Rehabil ; 100(8): 1458-1466, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30731067

RESUMO

OBJECTIVES: To investigate which clinical assessments are suitable for differentiating patients who fall from patients who do not fall in patients with idiopathic normal pressure hydrocephalus (iNPH). DESIGN: Prospective observational study. SETTING: Osaka Medical College Hospital. PARTICIPANTS: Patients with a cerebrospinal fluid tap test (TT) result meeting the diagnosis criteria for iNPH (N=68). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were assessed before the TT based on the following: timed Up and Go (TUG), 10-meter walk test (10MWT), Functional Gait Assessment (FGA), Berg Balance Scale (BBS), isometric quadriceps strength (QS), and a history of falls within the past 6 months. RESULTS: The full area under the curve (AUC) of the receiver operating characteristic curves and 95% confidence interval were found to be 0.651 (95% confidence interval, 0.503-0.775) for the TUG, 0.692 (95% confidence interval, 0.540-0.812) for the 10MWT, 0.869 (95% confidence interval, 0.761-0.933) for the FGA, and 0.796 (95% confidence interval, 0.663-0.886) for the BBS; except for QS, they all were identified as statistically significant predictive variables. In the TUG<20 seconds group (n=47), the FGA (AUC 0.849 [95% confidence interval, 0.698-0.932]) and BBS (AUC 0.734 [95% confidence interval, 0.550-0.862]) were found to be statistically significant predictive variables; however, the other assessments were not. In the TUG<15 seconds group (n=34), the FGA was found to be the only statistically significant predictive variable (AUC 0.842 [95% confidence interval, 0.640-0.942]), whereas the other assessments were not. The AUC of the FGA was statistically significantly greater than those of the other assessments. CONCLUSIONS: Our findings indicate that patients with iNPH who fall experience falls due to dynamic balance dysfunction during gait rather than lower limb muscle strength. The FGA may be more suitable than other assessments for differentiating patients who fall from patients who do not fall in patients with mild iNPH.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Avaliação da Deficiência , Transtornos Neurológicos da Marcha/fisiopatologia , Hidrocefalia de Pressão Normal/fisiopatologia , Equilíbrio Postural/fisiologia , Idoso , Feminino , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Masculino , Força Muscular/fisiologia , Estudos Prospectivos , Fatores de Risco
6.
J Clin Neurosci ; 61: 10-13, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30409528

RESUMO

Idiopathic Normal Pressure Hydrocephalus (iNPH) is a frequent neuropsychiatric entity. Clinically it is characterised by Hakim's triad: Dementia, gait disturbance and urinary incontinence. While its symptomatology is typical, the etiology and thereby physiopathology of iNPH still remain enigmatic. This review summarizes and synthesizes different etiologic conceptions and physiopathologic aspects of iNPH. A research of literature via the PubMed/MEDLINE and the Cochrane database was conducted. Only English language articles clearly outlining a reasonable concept of physiopathology were included. Most authors advocate that iNPH is a result of chronically altered cerebrospinal fluid (CSF) dynamics, i.e. deranged CSF production, kinetics and reabsorption. In addition, there are vascular, metabolo-neurodegenerative and hereditary factors. Neuroinflammation does not seem to play a significant role in the etiology of iNPH. All in all, iNPH seems to combine several pathogenetic factors leading to a self-reinforcing vicious circle. The majority of studies hint at CSF disturbances on grounds of altered hemodynamics.


Assuntos
Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/etiologia , Hidrocefalia de Pressão Normal/fisiopatologia , Feminino , Humanos , Masculino
8.
Acta Neuropathol Commun ; 6(1): 102, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270816

RESUMO

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropathology with unknown cause characterised by gait impairment, cognitive decline and ventriculomegaly. These patients often present comorbidity with Alzheimer's disease (AD), including AD pathological hallmarks such as amyloid plaques mainly consisting of amyloid ß-peptide and neurofibrillary tangles consisting of hyperphosphorylated tau protein. Even though some of the molecular mechanisms behind AD are well described, little is known about iNPH. Several studies have reported that mitochondria-endoplasmic reticulum contact sites (MERCS) regulate amyloid ß-peptide metabolism and conversely that amyloid ß-peptide can influence the number of MERCS. MERCS have also been shown to be dysregulated in several neurological pathologies including AD.In this study we have used transmission electron microscopy and show, for the first time, several mitochondria contact sites including MERCS in human brain biopsies. These unique human brain samples were obtained during neurosurgery from 14 patients that suffer from iNPH. Three of these 14 patients presented comorbidities with other dementias: one patient with AD, one with AD and vascular dementia and one patient with Lewy body dementia. Furthermore, we report that the numbers of MERCS are increased in biopsies obtained from patients diagnosed with dementia. Moreover, the presence of both amyloid plaques and neurofibrillary tangles correlates with decreased contact length between endoplasmic reticulum and mitochondria, while amyloid plaques alone do not seem to affect endoplasmic reticulum-mitochondria apposition. Interestingly, we report a significant positive correlation between the number of MERCS and ventricular cerebrospinal fluid amyloid ß-peptide levels, as well as with increasing age of iNPH patients.


Assuntos
Biópsia , Encéfalo/patologia , Encéfalo/ultraestrutura , Retículo Endoplasmático/metabolismo , Hidrocefalia de Pressão Normal/patologia , Mitocôndrias/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Precursor de Proteína beta-Amiloide/metabolismo , Retículo Endoplasmático/ultraestrutura , Feminino , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Masculino , Entrevista Psiquiátrica Padronizada , Microscopia Eletrônica de Transmissão , Mitocôndrias/ultraestrutura , Emaranhados Neurofibrilares/metabolismo , Emaranhados Neurofibrilares/patologia , Estatísticas não Paramétricas , Proteínas tau/metabolismo
9.
Sci Rep ; 8(1): 13639, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206302

RESUMO

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by reversible neurological symptoms due to an impairment in cerebrospinal fluid (CSF) clearance. In these patients, cognitive functions are severely impaired, with a scenario similar to Alzheimer's disease (AD), making the differential diagnosis difficult and highlighting the need of new markers. We analyzed the composition of sphingolipids (SLs) in serum, by combining a single phase extraction with a high-performance thin-layer chromatography (HPTLC) primuline-profiling, and, in CSF, by MALDI profiling and LC-MS. Ceramides and sphingomyelins (SMs) were similar in serum of iNPH and AD patients compared to healthy controls, whereas, in CSF, MALDI profiling indicated that: 1) SM C24:1 is significantly decreased in AD compared to iNPH patients and controls (Kruskal-Wallis p-value < 0.00001); 2) phosphatidylcholine (PC) 36:2 is increased in iNPH patients (p-value < 0.001). LC-MS identified an increasing trend of Cer C24:0 and of a set of SMs in patients with AD, a significant decrease of sphingosine-1-phosphate (S1P) (t-test p-value 0.0325) and an increase of glucosylceramide (GlcCer) C24:0 (p-value 0.0037) in AD compared to iNPH patients. In conclusion CSF PC 36:2, SM C24:1, S1P, and GlcCer can contribute to improve the differential diagnosis of patients with iNPH or AD and foster preventive therapeutic strategies in the early phase of the disease.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Esfingomielinas/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/fisiopatologia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Ceramidas/sangue , Ceramidas/líquido cefalorraquidiano , Disfunção Cognitiva/sangue , Disfunção Cognitiva/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Hidrocefalia de Pressão Normal/sangue , Hidrocefalia de Pressão Normal/fisiopatologia , Masculino , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Esfingomielinas/sangue
10.
Clin Neurol Neurosurg ; 174: 92-96, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30219624

RESUMO

OBJECTIVES: To determine which cognitive and upper limb assessments can identify change in patients undergoing a Cerebrospinal fluid (CSF) tap test (TT) diagnosed with idiopathic Normal Pressure Hydrocephalus (iNPH). PATIENTS AND METHODS: Prospective observational study of 74 iNPH patients undergoing a CSF TT for consideration of a ventricular peritoneal shunt. Patients who were offered surgical intervention were classified as responders. Patients were assessed with a battery of cognitive and upper limb assessments prior to and following a CSF TT. The Timed up and go cognition (TUG-C), Montreal Cognitive assessment (MoCA) and 9-hole peg test were utilised. RESULTS: 40 patients were classified responders. Significant differences were identified for responders for the MoCA (0.62 points) and TUG-C (-6.02 s). Only the executive function and orientation sub scores of the MoCA showed significant changes for responders. The 9 hole peg test mean change of 4.33 s for responders was not significant. Non-responder change scores for the MoCA (0.22 points), TUG-C (0.3 s) and 9 hole peg test (2.58 s) were not significant. CONCLUSION: The TUG-C has the potential to identify change in patients resulting from a CSF TT. While statistically significant change was found for the MoCA, a mean change of less than 1 point on this scale is unlikely to be clinically relevant. Similarly, the 9 hole peg test cannot be endorsed as an assessment tool for identifying changed performance in iNPH.


Assuntos
Cognição/fisiologia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Testes de Estado Mental e Demência , Punção Espinal/tendências , Extremidade Superior/fisiologia , Idoso , Idoso de 80 Anos ou mais , Função Executiva/fisiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Punção Espinal/efeitos adversos , Punção Espinal/métodos
11.
Neurol India ; 66(5): 1407-1412, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233015

RESUMO

Objectives: To compare the change in peak cerebrospinal (CSF) flow velocity at the cerebral aqueduct in patients with normal pressure hydrocephalus (NPH) before and after CSF tapping with clinical outcome of the patients, i.e., gait improvement. Materials and Methods: Forty patients with NPH were evaluated before and after CSF tapping on 3 consecutive days at our institution. Gait improvement was compared with the average peak velocity at the cerebral aqueduct. The average peak velocity was also compared before and after lumbar CSF tapping using phase contrast magnetic resonance imaging (PC-MRI). The different flow parameters were compared using paired t-test. Results: The average peak velocity before and after lumbar CSF tapping was 5.8196 ± 1.420 cm/s and 4.1411 ± 1.0638 cm/s, respectively. The peak positive, negative, and average velocity decreased in the post-tap group. In our study, 70% of the patients showed gait improvement, and a comparison of the gait improvement with the change in average peak velocity was statistically significant (P = 0.001). Comparison of the change in peak positive and negative velocity with gait improvement was also statistically significant, with a P value of 0.004 and <0.001, respectively. Rest of the CSF flow parameters were statistically insignificant. Conclusion: PC-MRI is a sensitive method to support the diagnosis of NPH. Different flow parameters were comparable before and after CSF tapping. The parameters which might be useful for assessing clinical improvement include a change in the peak average, as well as positive, and negative velocity.


Assuntos
Aqueduto do Mesencéfalo/diagnóstico por imagem , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Neuroimage Clin ; 20: 731-741, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30238917

RESUMO

The aim of the present study was to examine cerebrospinal fluid (CSF) volumetric net flow rate and direction at the cranio-cervical junction (CCJ) and cerebral aqueduct in individuals with idiopathic normal pressure hydrocephalus (iNPH) using cardiac-gated phase-contrast magnetic resonance imaging (PC-MRI). An in-depth, pixel-by-pixel analysis of regions of interest from the CCJ and cerebral aqueduct, respectively, was done in 26 iNPH individuals, and in 4 healthy subjects for validation purposes. Results from patients were compared with over-night measurements of static and pulsatile intracranial pressure (ICP). In iNPH, CSF net flow at CCJ was cranially directed in 17/22 as well as in 4/4 healthy subjects. Estimated daily CSF volumetric net flow rate at CCJ was 6.9 ±â€¯9.9 L/24 h in iNPH patients and 4.5 ±â€¯5.0 L/24 h in healthy individuals. Within the cerebral aqueduct, the CSF net flow was antegrade in 7/21 iNPH patients and in 4/4 healthy subjects, while it was retrograde (i.e. towards ventricles) in 14/21 iNPH patients. Estimated daily CSF volumetric net flow rate in cerebral aqueduct was 1.1 ±â€¯2.2 L/24 h in iNPH while 295 ±â€¯53 mL/24 h in healthy individuals. Magnitude of cranially directed CSF net flow in cerebral aqueduct was highest in iNPH individuals with signs of impaired intracranial compliance. The study results indicate CSF flow volumes and direction that are profoundly different from previously assumed. We hypothesize that spinal CSF formation may serve to buffer increased demand for CSF flow through the glymphatic system during sleep and during deep inspiration to compensate for venous outflow.


Assuntos
Ventrículos Cerebrais/fisiopatologia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/fisiopatologia , Adulto , Idoso , Aqueduto do Mesencéfalo/diagnóstico por imagem , Aqueduto do Mesencéfalo/fisiopatologia , Ventrículos Cerebrais/diagnóstico por imagem , Feminino , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética , Masculino , Canal Vertebral/diagnóstico por imagem , Canal Vertebral/fisiopatologia
13.
J Alzheimers Dis ; 66(1): 319-331, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30248058

RESUMO

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is commonly treated by cerebrospinal fluid (CSF) shunting. However, the long-term efficacy of shunt intervention in the presence of comorbid Alzheimer's disease (AD) pathology is debated. OBJECTIVE: To identify AD-associated CSF biomarkers predictive of shunting surgery outcomes in patients with iNPH. METHODS: Preoperative levels of total and phosphorylated Tau (p-Tau) were measured in 40 patients with iNPH divided into low (<30 pg/mL) and high (≥30 pg/mL) p-Tau groups and followed up for three years after lumboperitoneal shunting. The modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Frontal Assessment Battery, and iNPH Grading Scale scores were compared between the age-adjusted low (n = 24; mean age 75.7 years [SD 5.3]) and high (n = 11; mean age 76.0 years [SD 5.6]) p-Tau groups. RESULTS: Cognitive function improved early in the low p-Tau group and was maintained thereafter (p = 0.005). In contrast, the high p-Tau group showed a gradual decline to baseline levels by the third postoperative year (p = 0.040). Although the p-Tau concentration did not correlate with the preoperative MMSE score, a negative correlation appeared and strengthened during follow-up (R2 = 0.352, p < 0.001). Furthermore, the low p-Tau group showed rapid and sustained mRS grade improvement, whereas mRS performance gradually declined in the high p-Tau group. CONCLUSIONS: Preoperative CSF p-Tau concentration predicted some aspects of cognitive function after shunt intervention in patients with iNPH. The therapeutic effects of shunt treatment were shorter-lasting in patients with coexisting AD pathology.


Assuntos
Cognição/fisiologia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/cirurgia , Cuidados Pré-Operatórios/métodos , Derivação Ventriculoperitoneal/tendências , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Hidrocefalia de Pressão Normal/psicologia , Masculino , Pessoa de Meia-Idade , Fosforilação/fisiologia , Prognóstico , Fatores de Tempo
14.
Neurología (Barc., Ed. impr.) ; 33(7): 449-458, sept. 2018. ilus
Artigo em Espanhol | IBECS | ID: ibc-175953

RESUMO

Introducción: Desde la descripción hace 5 décadas de la hidrocefalia crónica del adulto idiopática (HCAi), su fisiopatología ha sido considerada básicamente relacionada con el efecto que la dilatación ventricular ejerce sobre las estructuras adyacentes al sistema ventricular. Sin embargo, las alteraciones en el flujo sanguíneo cerebral (FSC) y, sobre todo, la reducción en el recambio licuoral parecen emerger como componentes fisiopatológicos principales de esta enfermedad. Desarrollo: En la HCAi se observa una compresión del tracto piramidal, de los circuitos cortico-subcorticales fronto-estriatales y fronto-reticulares, y de las fibras profundas del fascículo longitudinal superior. En el cuerpo calloso se objetiva un descenso en el número de fibras comisurales, que son reemplazadas por gliosis. El FSC se encuentra alterado, con un patrón de última pradera en la región subcortical adyacente a los ventrículos, correspondiente a la intersección entre las arterias subependimarias y las arterias perforantes dependientes de los grandes troncos arteriales de la circulación anterior. El recambio diario del LCR se ve disminuido en un 75%, lo que conlleva una reducción del aclaramiento de neurotóxicos y la interrupción de las señalizaciones neuroendocrinas y paracrinas que ocurren a través del LCR. Conclusiones: La HCAi emerge como una entidad nosológica compleja, en la que los efectos de la microangiopatía subcortical y la disminución del recambio de LCR desempeñan un papel fundamental. Esta base fisiopatológica aleja la HCAi del concepto clásico de hidrocefalia y la acerca al perfil de otras enfermedades neurodegenerativas, como la enfermedad de Alzheimer o la enfermedad de Binswanger


Introduction: Since its description five decades ago, the pathophysiology of idiopathic chronic adult hydrocephalus (iCAH) has been traditionally related to the effect that ventricular dilatation exerts on the structures surrounding the ventricular system. However, altered cerebral blood flow, especially a reduction in the CSF turnover rate, are starting to be considered the main pathophysiological elements of this disease. Development: Compression of the pyramidal tract, the frontostriatal and frontoreticular circuits, and the paraventricular fibres of the superior longitudinal fasciculus have all been reported in iCAH. At the level of the corpus callosum, gliosis replaces a number of commissural tracts. Cerebral blood flow is also altered, showing a periventricular watershed region limited by the subependymal arteries and the perforating branches of the major arteries of the anterior cerebral circulation. The CSF turnover rate is decreased by 75%, leading to the reduced clearance of neurotoxins and the interruption of neuroendocrine and paracrine signalling in the CSF. Conclusions: iCAH presents as a complex nosological entity, in which the effects of subcortical microangiopathy and reduced CSF turnover play a key role. According to its pathophysiology, it is simpler to think of iCAH more as a neurodegenerative disease, such as Alzheimer disease or Binswanger disease than as the classical concept of hydrocephalus


Assuntos
Humanos , Hidrocefalia de Pressão Normal/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Ventrículos Cerebrais/fisiopatologia , Pressão do Líquido Cefalorraquidiano/fisiologia , Circulação Cerebrovascular/fisiologia , Doença Crônica , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Doenças Neurodegenerativas/líquido cefalorraquidiano , Doenças Neurodegenerativas/diagnóstico
15.
JCI Insight ; 3(13)2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29997300

RESUMO

To what extent does the subarachnoid cerebrospinal fluid (CSF) compartment communicate directly with the extravascular compartment of human brain tissue? Interconnection between the subarachnoid CSF compartment and brain perivascular spaces is reported in some animal studies, but with controversy, and in vivo CSF tracer studies in humans are lacking. In the present work, we examined the distribution of a CSF tracer in the human brain by MRI over a prolonged time span. For this, we included a reference cohort, representing close to healthy individuals, and a cohort of patients with dementia and anticipated compromise of CSF circulation (idiopathic normal pressure hydrocephalus). The MRI contrast agent gadobutrol, which is confined to the extravascular brain compartment by the intact blood-brain barrier, was used as a CSF tracer. Standardized T1-weighted MRI scans were performed before and after intrathecal gadobutrol at defined time points, including at 24 hours, 48 hours, and 4 weeks. All MRI scans were aligned and brain regions were segmented using FreeSurfer, and changes in normalized T1 signals over time were quantified as percentage change from baseline. The study provides in vivo evidence of access to all human brain subregions of a substance administered intrathecally. Clearance of the tracer substance was delayed in the dementia cohort. These observations translate previous findings in animal studies into humans and open new prospects concerning intrathecal treatment regimens, extravascular contrast-enhanced MRI, and assessment of brain clearance function.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Líquido Cefalorraquidiano/metabolismo , Sistema Glinfático/metabolismo , Imagem por Ressonância Magnética/métodos , Doença de Alzheimer , Animais , Meios de Contraste , Demência , Líquido Extracelular/metabolismo , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Pressão Intracraniana , Compostos Organometálicos/farmacologia
16.
Clin Chim Acta ; 486: 1-7, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30003878

RESUMO

BACKGROUND: The complement system is a functional link between the innate and adaptive immune system and present in all compartments of the body. The composition of the cerebrospinal fluid (CSF) differs between the ventricular, cisternal and lumbar space. Usually, concentrations of blood-derived CSF proteins increase from ventricular to lumbar fractions. METHODS: In 20 geriatric patients with suspected normal pressure hydrocephalus (NPH) [13 women, 7 men, age 80.5 (75/85) years; median (25th/75th percentile)] a lumbar spinal tap of 40 ml was performed, and 10 ml of serum was drawn. CSF, sequentially collected in 8 fractions of 5 ml (1st fraction: lumbar CSF; 8th fraction: cisterna magna-near CSF), was analyzed for complement protein C3, and the activation products C3a and sC5b-9 by enzyme immunoassay. RESULTS: The concentrations of the complement factors measured in fractions 1 and 8 of each individual patient were strongly correlated: C3 (Spearman's rank correlation coefficient rS = 0.75, p = 0.0002); C3a (rS = 0.93, p < 0.0001); sC5b-9 (rS = 0.64, p = 0.002). CSF complement concentrations were lower in the cistern-near fraction 8 than in the lumbar fraction 1 (C3: p = 0.005; C3a: p = 0.0009; sC5b-9: p = 0.0003, Wilcoxon signed rank test). The concentrations of complement factors in CSF were two orders of magnitude lower than those in serum. C3 levels in the lumbar CSF strongly correlated with the lumbar CSF/serum albumin concentration quotient (QAlb) as a measure of the functionability of the blood-CSF barrier and the velocity of CSF flow (rS = 0.84, p < 0.0001) suggesting diffusion of C3 from blood to CSF. The lumbar and cistern-near concentrations of C3a did not significantly correlate with QAlb (rS = 0.26) pointing to a local conversion of C3 to C3a. The lumbar concentrations of sC5b-9 moderately correlated with QAlb (rS = 0.62, p = 0.004). Plotting the CSF/serum quotient of C3 and sC5b-9 versus the QAlb revealed an approx. 50% local synthesis of C3, but a strong production of sC5b-9 in the CNS. CONCLUSIONS: The increase of the complement concentrations from cisternal to lumbar CSF and the strong correlation of C3 with QAlb suggest that (1) a substantial portion of complement C3 in CSF originates from blood and (2) the complement system is mildly activated in the CSF of NPH patients.


Assuntos
Ativação do Complemento/imunologia , Avaliação Geriátrica , Hidrocefalia de Pressão Normal/epidemiologia , Hidrocefalia de Pressão Normal/imunologia , Vértebras Lombares/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Técnicas Imunoenzimáticas , Masculino
17.
J Alzheimers Dis ; 64(1): 171-179, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29865068

RESUMO

BACKGROUND: Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo. OBJECTIVE: Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in brain biopsy. METHODS: Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF Aß1 - 42, total tau, and P-tau181 measures, underwent brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging. RESULTS: Seven patients had amyloid-ß (Aß, 4G8) plaques, two both Aß and phosphorylated tau (Pτ, AT8) and one only Pτ in biopsy. As expected, increased brain biopsy Aß was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either brain biopsy Pτ or CSF P-tau181 or total tau. CONCLUSIONS: S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aß and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.


Assuntos
Compostos de Anilina/farmacocinética , Encéfalo , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Placa Amiloide/metabolismo , Quinolinas/farmacocinética , Tiazóis/farmacocinética , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Mapeamento Encefálico , Feminino , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons
18.
Arq Neuropsiquiatr ; 76(5): 324-331, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29898079

RESUMO

INTRODUCTION: Normal pressure hydrocephalus (NPH), described by Hakim and Adams in 1965, is characterized by gait apraxia, urinary incontinence, and dementia. It is associated with normal cerebrospinal fluid (CSF) pressure and ventricular dilation that cannot be attributed to cerebral atrophy. OBJECTIVES: To evaluate gait characteristics in patients with idiopathic NPH and investigate the effect of the CSF tap test (CSF-TT) on gait. METHODS: Twenty-five patients diagnosed with probable idiopathic NPH were submitted to the CSF-TT. The procedure aimed to achieve changes in gait parameters. RESULTS: Fifteen gait parameters were assessed before and after the CSF-TT. Five showed a statistically significant improvement (p < 0.05): walking speed (p < 0.001), cadence (p < 0.001), step length (p < 0.001), en bloc turning (p = 0.001), and step height (p = 0.004). CONCLUSION: This study demonstrated that gait speed was the most responsive parameter to the CSF-TT, followed by cadence, step length, en bloc turning, and step height.


Assuntos
Apraxia da Marcha/diagnóstico , Hidrocefalia de Pressão Normal/complicações , Idoso , Idoso de 80 Anos ou mais , Pressão do Líquido Cefalorraquidiano , Feminino , Apraxia da Marcha/líquido cefalorraquidiano , Apraxia da Marcha/etiologia , Apraxia da Marcha/fisiopatologia , Avaliação Geriátrica , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/fisiopatologia , Masculino , Estudos Prospectivos
19.
Arch Phys Med Rehabil ; 99(11): 2244-2250, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29702069

RESUMO

OBJECTIVES: To identify in patients with idiopathic normal pressure hydrocephalus (iNPH) undergoing a cerebrospinal fluid (CSF) tap test (TT) for consideration of a ventricular peritoneal (VP) shunt: (1) gait and balance measures, which identify symptom change; (2) differences present between pre- and post-CSF TT scores between patients classified as responders and nonresponder; (3) ability of patients with iNPH to accurately quantify change in their gait and balance symptoms from a CSF TT. DESIGN: Prospective observational study. Post-CSF TT assessment was completed 2-4 hours post. SETTING: Tertiary referral neurological and neurosurgical hospital. PARTICIPANTS: Patients (N=74) with iNPH receiving a 30 mL CSF TT for consideration of a VP shunt. INTERVENTIONS: Patients underwent a battery of gait and balance measures pre- and post-CSF TT and indicated their perceived change on a global rating of change (GRC). Patients deemed to improve and offered VP shunt insertion by a neurologist or neurosurgeon were labeled responders. MAIN OUTCOME MEASURES: Performance oriented mobility assessment (Tinetti), Berg Balance Scale (BBS), timed Up and Go (TUG), 10-meter walk test (10MWT), GRC. RESULTS: Forty patients were classified responders, 34 nonresponders. Significant differences were identified for responders: Tinetti (3.88 points), TUG (3.98 seconds), 10MWT (0.08 m/sec), and BBS (5.29 points). Significant differences were found for nonresponders for the Tinetti (0.91 points) and BBS (2.06 points). Change scores for responders and nonresponders were significantly different for all tests between responders and nonresponders. GRC scores for gait (+2 for responders, 0 for nonresponders) and balance (+2.5 for responders, 0 for nonresponders) were both significantly different. CONCLUSIONS: The Tinetti, BBS, and TUG can identify change in patients undergoing a CSF TT for iNPH. Patients appear to be able to accurately identify if change has occurred.


Assuntos
Análise da Marcha/estatística & dados numéricos , Transtornos Neurológicos da Marcha/diagnóstico , Hidrocefalia de Pressão Normal/fisiopatologia , Seleção de Pacientes , Punção Espinal/métodos , Idoso , Idoso de 80 Anos ou mais , Derivações do Líquido Cefalorraquidiano , Avaliação da Deficiência , Feminino , Análise da Marcha/métodos , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/cirurgia , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/complicações , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Estudos Prospectivos , Teste de Caminhada/métodos , Teste de Caminhada/estatística & dados numéricos
20.
J Neurol Sci ; 387: 21-26, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29571865

RESUMO

INTRODUCTION: Idiopathic normal pressure hydrocephalus (INPH) is known to be a potentially treatable neurologic condition. The neurocognitive outcomes after surgery, however, have been variable. It is important to define preoperative characteristics of patients that predicts the shunting outcome. We aimed to compare baseline differences between shunt-responsive and unresponsive patients after 1year from surgery in order to identify preoperative predictors showing favorable clinical outcomes. METHODS: Among 69 candidates, 31 patients with probable INPH completed the study. Patients were divided into two groups, responsive group (n=17) and unresponsive group (n=14), according to the clinical outcomes on INPH grading scale and modified Rankin score (MRS). Preoperative cerebrospinal (CSF) Aß, tau levels, MRI findings, and clinical characteristics were compared between the groups. Correlations between shunt responsiveness and preoperative characteristics were also assessed. RESULTS: After 1year from shunt, gait problem was the most likely to improve. Shunt-responsive group showed lower CSF p-tau/Aß, fewer lacunes, and higher incidence of disproportionately enlarged subarachnoid space (DESH) signs on MRIs compared to those in unresponsive group. Favorable outcome was related with positive DESH sign and fewer lacunes. CONCLUSIONS: Our results suggest that biomarkers representing non-INPH related pathology including Alzheimer's disease and small vessel disease might show less favorable clinical outcomes after 1year from surgery.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Transtornos Neurológicos da Marcha/terapia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/cirurgia , Derivação Ventriculoperitoneal/métodos , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Período Pré-Operatório , Estudos Retrospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
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