RESUMO
We sought to describe the cognitive profile of patients with Idiopathic Normal Pressure Hydrocephalus (iNPH) using a comprehensive neuropsychological battery. Based on age and education correlated norms, we aimed to compare performance in each measured cognitive domain: executive functions (EFs), verbal memory (VM), non-verbal memory (nVM), visuoconstructional abilities (VA) and attention/psychomotor speed (A/PS). Patients diagnosed with iNPH underwent comprehensive neuropsychological evaluation before shunting. Their performance was compared to the age and education correlated norms. Correlation of different cognitive domains in iNPH profile was performed. A total of 53 iNPH patients (73.21 ± 5.48 years) were included in the study. All of the measured cognitive domains were significantly damaged. The most affected domains were EFs and VM (p<0.001 and p<0.001, respectively). A/PS domain was affected milder than EFs and VM (p<0.001). The least affected domains were nVM (p<0.001) and VA (p<0.001). Patients with iNPH are affected in all cognitive domains and the cognitive decline is uneven across these domains. The impairment of memory was shown to depend on the presented material. VM was shown to be much more severely affected than nVM and along with VM, EFs were shown to be the most affected. A/PS speed was shown to be less affected than VM and EFs and the least affected domains were nVM and VA.
Assuntos
Disfunção Cognitiva , Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Função Executiva , Testes Neuropsicológicos , CogniçãoRESUMO
While the cause of altered mentation in the elderly may be multifactorial, infectious etiologies may be missed. This case report aims to detail an account of a patient with dementia, found to have Lyme meningitis in the setting of a normal pressure hydrocephalus (NPH). The patient smelled of urine and presented with ambulatory dysfunction, fitting the "wet, wacky, and wobbly" triad of NPH while also having subjective chills and leukocytosis. Non-contrast brain CT scan showed dilated ventricles. Cerebrospinal fluid (CSF) studies suggested aseptic meningitis. Serum studies using a modified two-tiered algorithm confirmed the diagnosis of Lyme disease. Treatment of the underlying condition with a prolonged course of doxycycline improved symptoms and clinical course. Review of the literature on the association between Lyme meningitis and NPH reveals that few cases of Lyme-related NPH have been reported worldwide and further research into the pathophysiology, diagnostic approach, treatment modalities, and management of NPH secondary to Lyme meningitis may be warranted.
Assuntos
Demência , Hidrocefalia de Pressão Normal , Doença de Lyme , Meningite , Humanos , Idoso , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Encéfalo , Doença de Lyme/complicações , Doença de Lyme/diagnóstico , Meningite/complicações , Meningite/diagnóstico , Demência/complicações , Demência/diagnósticoRESUMO
Idiopathic normal pressure hydrocephalus (iNPH) is an often-overlooked or misdiagnosed brain disorder characterized by overt ventriculomegaly and associated with gait disturbances, cognitive impairment, and urinary incontinence. If correctly diagnosed, it is considered the only form of dementia treatable with surgery, namely through a ventriculoperitoneal or ventriculoatrial shunt with programmable valves.Among the 856 spinal and ventricular infusion tests performed from 2001 to 2017 at our institution, we analyzed 106 cases selected for suspected normotensive hydrocephalus. In all cases, Intracranial Elastance Index (IEI) and outflow resistance (Rout) values were calculated: 52 of these patients underwent Spinal Katzman Test (SKT), and the remaining 54 underwent an intraventricular infusion test (IVKT). Of the 40 patients in the SKT group with pathological elastance (71%), 17 also had a Rout >12 mmHg and 23 a Rout <12 mmHg. Of the 50 patients in the IVKT group with pathological elastance (92%), 38 also had a Rout >12 mmHg and 12 a Rout <12 mmHg.IVKT and SKT to date represent two useful tools in the diagnosis of normal pressure hydrocephalus. Despite being more invasive, IVKT, including both the intracranial elastance index (IEI) and Rout analysis, could be considered more reliable than SKT and therefore could be reserved for the most controversial cases.
Assuntos
Encefalopatias , Disfunção Cognitiva , Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Infusão Espinal , EncéfaloRESUMO
Japanese guidelines for idiopathic normal pressure hydrocephalus (iNPH) (iNPHGL) are the first and only guidelines in the world that were revised following subsequent developments in iNPH research. We first discuss the virtuous cycle in which the development and revision of the iNPHGL and how the implementation of two consecutive multicenter prospective studies conducted in Japan, SINPHONIs, have worked together to advance iNPH practices. Subsequently, we explained the most characteristic features of the iNPHGL, such as "Positioning of iNPH," "Diagnostic Criteria," and "Algorithms for Diagnosis and Treatment." To classify iNPH, we categorized chronic adult-onset normal pressure hydrocephalus (NPH) as iNPH, secondary NPH, Congenital/Developmental NPH, and Familial NPH. In the diagnostic criteria and algorithm, we classified iNPH into four categories: Suspected iNPH, Possible iNPH, Probable iNPH, and Definite iNPH, depending on the certainty of the diagnosis. In addition, a positioned disproportionately enlarged subarachnoid space hydrocephalus (DESH) on head computed tomography and magnetic resonance imaging is an important finding for the diagnosis of iNPH. Finally, we presented the results of a survey on the treatment status of patients with suspected iNPH, awareness of DESH, and use of this iNPHGL among medical centers for dementia in Japan.
Assuntos
Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/terapia , Estudos Prospectivos , Imageamento por Ressonância Magnética , Neuroimagem , JapãoRESUMO
Although the pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain largely unknown, it is well acknowledged that iNPH causes ventricular enlargement due to decreased cerebrospinal fluid (CSF) absorption. Pathophysiologically, it is supposed that the excretion of waste proteins is impaired along with CSF. Hence, they tend to aggregate, and in many neurodegenerative diseases, abnormal aggregation and accumulation of such proteins are deeply involved in the pathogenesis of disease. Biomarkers (BMs) contribute to diagnosis by identifying comorbid neurodegenerative diseases that may affect the prognosis of treatment, as well as exploring the pathogenetic mechanisms of iNPH. In addition, BMs can be an important prognostic test for shunt therapy.
Assuntos
Hidrocefalia de Pressão Normal , Doenças Neurodegenerativas , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Biomarcadores , Prognóstico , ProteínasRESUMO
OBJECTIVE: To determine the utility of symptoms, signs, comorbidities and background variables for the prediction of outcome of treatment in iNPH. METHODS: A prospective observational study of consecutively included iNPH patients, who underwent neurological, physiotherapeutic and neuropsychological assessments before and after shunt surgery. The primary outcome measure was the total change on the iNPH scale, and patients were defined as improved postoperatively if they had improved by at least five points on that scale. RESULTS: 143 iNPH patients were included, and 73% of those were improved after surgery. None of the examined symptoms or signs could predict which patients would improve after shunt surgery. A dominant subjective complaint of memory problems at baseline was predictive of non-improvement. The reported comorbidities, duration of symptoms and BMI were the same in improved and non-improved patients. Each of the symptom domains (gait, neuropsychology, balance, and continence) as well as the total iNPH scale score improved significantly (from median 53 to 69, p < 0.001). The proportions of patients with shuffling gait, broad-based gait, paratonic rigidity and retropulsion all decreased significantly. DISCUSSION: This study confirms that the recorded clinical signs, symptoms, and impairments in the adopted clinical tests are characteristic findings in iNPH, based on that most of them improved after shunt surgery. However, our clinical data did not enable predictions of whether patients would respond to shunt surgery, indicating that the phenotype is unrelated to the reversibility of the iNPH state and should mainly support diagnosis. Absence of specific signs should not be used to exclude patients from treatment.
Assuntos
Hidrocefalia de Pressão Normal , Humanos , Feminino , Masculino , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/diagnóstico , Idoso , Estudos Prospectivos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Testes Neuropsicológicos , Pessoa de Meia-IdadeRESUMO
Patients diagnosed with low-pressure hydrocephalus typically present with enlarged ventricles and unusually low intracranial pressure, often measuring below 5 cmH2O or even below atmospheric pressure. This atypical presentation often leads to low recognition and diagnostic rates. The development of low-pressure hydrocephalus is believed to be associated with a decrease in the viscoelasticity of brain tissue or separation between the ventricular and subarachnoid spaces. Risk factors for low-pressure hydrocephalus include subarachnoid hemorrhage, aqueduct stenosis, prior cranial radiotherapyï¼ ventricular shunting, and cerebrospinal fluid leaks. For potential low-pressure hydrocephalus, diagnostic criteria include neurological symptoms related to hydrocephalus, an Evans index >0.3 on imaging, ICP ≤ 5 cm H2O, symptom improvement with negative pressure drainage, and exclusion of ventriculomegaly caused by neurodegenerative diseases. The pathogenesis and pathophysiological features of low-pressure hydrocephalus differ significantly from other types of hydrocephalus, making it challenging to restore normal ventricular morphology through conventional drainage methods. The primary treatment options for low-pressure hydrocephalus involve negative pressure drainage and third ventriculostomy. With appropriate treatment, most patients can regain their previous neurological function. However, in most cases, permanent shunt surgery is still necessary. Low-pressure hydrocephalus is a rare condition with a high rate of underdiagnosis and mortality. Early identification and appropriate intervention are crucial in reducing complications and improving prognosis.
Assuntos
Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/terapia , Hidrocefalia de Pressão Normal/diagnóstico , Gerenciamento Clínico , Hidrocefalia/terapia , Hidrocefalia/etiologia , Hidrocefalia/diagnósticoRESUMO
According to a cohort study in a Japanese rural area, the prevalence of idiopathic normal pressure hydrocephalus (iNPH) in the 80s was 7.7% among the older inhabitants, despite only a small percentage of the population seeking consultation. The 16-year observation of the cohort revealed that people were in the state of asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging or asymptomatic ventricular enlargement several years before presenting symptoms and intracranial changes of iNPH. SFMBT1 was found to be a risk gene for iNPH, and investigating these risk genes will further the study of iNPH pathophysiology.
Assuntos
Hidrocefalia de Pressão Normal , Humanos , Estudos de Coortes , Hidrocefalia de Pressão Normal/epidemiologia , Hidrocefalia de Pressão Normal/genética , Hidrocefalia de Pressão Normal/diagnóstico , Imageamento por Ressonância Magnética , PrevalênciaRESUMO
Idiopathic normal pressure hydrocephalus (iNPH) is a clinical condition characterized by symptoms of gait disturbance, cognitive dysfunction, and urinary disturbance. In contrast, progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease characterized by supranuclear gaze palsy, akinetic rigidity, gait disturbance, and dementia. PSP manifests various clinical phenotypes that mimic other diseases and occasionally present iNPH-like presentations. Our previous publication showed that PSP develops iNPH-like magnetic resonance imaging (MRI) features more frequently than other neurodegenerative diseases. It is thus sometimes challenging to distinguish iNPH from PSP. Recently, we showed that patients with PSP, particularly those with iNPH-like MRI findings, often demonstrate amelioration of their gait disturbance following a spinal tap or shunt operation. Moreover, our study revealed that both patients with iNPH and PSP often manifest a placebo effect that can be evaluated by implementing a sham spinal tap. Therefore, although a positive response to a spinal tap has been thought of as a distinct feature of iNPH, it may not be useful in differentiating iNPH and PSP. However, in clinical practice, comparing the response to a spinal tap with that of a sham spinal tap may help accurately specify patients with iNPH or PSP who definitively respond to the shunt operation.
Assuntos
Hidrocefalia de Pressão Normal , Doenças Neurodegenerativas , Paralisia Supranuclear Progressiva , Humanos , Paralisia Supranuclear Progressiva/diagnóstico , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Imageamento por Ressonância MagnéticaRESUMO
Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (nâ=â19) and reliable (nâ=â43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-ß (Aß) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aß42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment?
Assuntos
Hidrocefalia de Pressão Normal , Testes Neuropsicológicos , Testes de Campo Visual , Humanos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/psicologia , Hidrocefalia de Pressão Normal/complicações , Feminino , Masculino , Idoso , Tomografia de Coerência Óptica , Reprodutibilidade dos Testes , Idoso de 80 Anos ou mais , Campos Visuais/fisiologia , Pessoa de Meia-Idade , Cognição/fisiologiaRESUMO
Neurosarcoidosis (NS) is a rare subtype of sarcoidosis with a poor prognosis and diverse clinical presentations that often poses a diagnostic and therapeutic challenge. We describe the case of a 53-year-old male with an initial diagnosis of lingual sarcoidosis, who subsequently developed ataxia and rapidly progressive cognitive impairment. A lumbar puncture revealed hypoglycorrhachia, hyperproteinorrachia, lymphocytic pleocytosis, and elevated IL-6 levels (600 pg/ml). Cerebrospinal fluid flow cytometry showed an elevated CD4 lymphocyte concentration and a CD4+/CD8+ ratio of 3.91, indicative of NS. Brain MRI showed hyperintense periventricular and subcortical lesions on FLAIR/T2 resembling progressive multifocal leukoencephalopathy (PML), although negative PCR for JC virus ruled out the differential diagnosis. Following a favorable evolutionary course with corticosteroid pulses, the patient relapsed with normotensive hydrocephalus, treated with immunosuppressants and ventriculoperitoneal shunting with a good response to date. This case underscores the importance of maintaining a high index of suspicion for NS in individuals with sarcoidosis and neurologic symptoms. In these cases, cerebrospinal fluid biomarkers such as IL-6 and CD4+/CD8+ ratio are essential to guide the diagnosis. Furthermore, it highlights that hydrocephalus is a rare complication and requires a multidisciplinary approach, including medical and neurosurgical treatment.
La neurosarcoidosis es un subtipo raro de sarcoidosis con mal pronóstico y diversas presentaciones clínicas que a menudo plantea un reto diagnóstico y terapéutico. Describimos el caso de un varón de 53 años con diagnóstico inicial de sarcoidosis lingual, que posteriormente desarrolló ataxia y deterioro cognitivo de rápida evolución. Una punción lumbar reveló hipoglucorraquia, hiperproteinorraquia, pleocitosis linfocítica y niveles elevados de IL-6 (600 pg/ml). La citometría de flujo del líquido cefalorraquídeo mostró una concentración elevada de linfocitos CD4 y un cociente CD4+/CD8+ de 3.91, indicativo de neurosarcoidosis. La RM cerebral evidenció lesiones hiperintensas periventriculares y subcorticales en FLAIR/T2 que se asemejaban a una leucoencefalopatía multifocal progresiva (LMP), aunque la PCR negativa para el virus JC descartó el diagnóstico diferencial. Tras un curso evolutivo favorable con pulsos de corticoides, el paciente recayó con hidrocefalia normotensiva, tratada con inmunosupresores y derivación ventriculoperitoneal con buena respuesta hasta la fecha. Este caso subraya la importancia de mantener un alto índice de sospecha de neurosarcoidosis en individuos con sarcoidosis y síntomas neurológicos. En estos casos, los biomarcadores del líquido cefalorraquídeo tales como la IL-6 y el cociente CD4+/CD8+ son esenciales para orientar el diagnóstico. Además, destaca que la hidrocefalia es una complicación poco frecuente y requiere un abordaje multidisciplinario, que incluya tratamiento médico y neuroquirúrgico.
Assuntos
Doenças do Sistema Nervoso Central , Demência , Hidrocefalia de Pressão Normal , Sarcoidose , Humanos , Masculino , Sarcoidose/complicações , Sarcoidose/diagnóstico , Pessoa de Meia-Idade , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Doenças do Sistema Nervoso Central/complicações , Demência/etiologia , Imageamento por Ressonância Magnética , Progressão da Doença , Diagnóstico DiferencialRESUMO
Idiopathic normal pressure hydrocephalus causes a triad of gait disturbance, dementia, and urinary incontinence in the elderly. All these symptoms may manifest as age-related functional decline or from neurological and non-neurological diseases common in the elderly. In idiopathic normal pressure hydrocephalus, characterized by ataxic-ataxic gait, subcortical dementia, and urge urinary incontinence, it is clinically important to consider these characteristic features. This overview describes the symptomatology of idiopathic normal pressure hydrocephalus.
Assuntos
Demência , Hidrocefalia de Pressão Normal , Hidrocefalia , Transtornos dos Movimentos , Incontinência Urinária , Humanos , Idoso , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/etiologia , Hidrocefalia/complicações , Demência/complicações , Transtornos dos Movimentos/complicações , Incontinência Urinária/diagnóstico , Incontinência Urinária/complicações , MarchaRESUMO
OBJECTIVE: Patients diagnosed with idiopathic Normal Pressure Hydrocephalus (iNPH) typically experience symptom improvements after undergoing a cerebrospinal fluid-tap test (CSF-TT), These improvements are recognized as indicative of potential improvements following surgical intervention. As gait disturbance is the most common iNPH symptom, gait improvements are of predominant interest. The purpose of this study was to examine if clinically important changes in gait and balance from CSF-TT predict meaningful changes following surgery. METHOD: The study involved analysis of data collected in a prospective observational study for 34 iNPH patients who underwent a CSF-TT and subsequent surgery. Linear regression, logistic regression and classification trees were used for predictive modelling comparing changes from CSF-TT with post-surgical changes in Tinetti, Timed Up and Go (TUG) and Berg Balance Scale (BBS) outcomes. RESULTS: Predictive models for minimal clinically important differences (MCIDs) from CSF-TT to surgery were significant for Tinetti (odds ratio = 1.42, p = 0.02) and BBS (odds ratio = 1.57, p < 0.01). Four items on Tinetti and two items on BBS were identified with a predictive accuracy of 79% and 76% respectively. BBS has the highest sensitivity (85%) and negative predictive value (77%). TUG had a 100% specificity and 100% positive predictive value. The predictive model using MCIDs for TUG was not significant (odds ratio = 1.13, p = 0.06). CONCLUSION: Clinically important changes from CSF-TT are useful in predicting post-surgical outcomes in iNPH patients. Tinetti and BBS, both have predictive value using MCID scores as cut off values, of which BBS is a stronger outcome measure for prediction.
Assuntos
Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/fisiopatologia , Feminino , Masculino , Idoso , Estudos Prospectivos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Equilíbrio Postural/fisiologia , Punção Espinal/métodos , Valor Preditivo dos Testes , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/diagnóstico , Transtornos Neurológicos da Marcha/fisiopatologia , Pessoa de Meia-IdadeRESUMO
A woman in her 70s presented with approximately 2 years of sudden-onset gait and cognitive problems. She had been diagnosed with normal pressure hydrocephalus (NPH) and underwent ventriculoperitoneal shunt (VPS) placement 1 year prior. Before VPS placement, brain imaging showed ventriculomegaly and chronic infarction of the right putamen and claustrum. A lumbar drain trial resulted in modest improvement of gait dysfunction. She underwent VPS placement for suspected NPH, but her symptoms remained unchanged. Examination revealed mild cognitive impairment, left-sided and lower body predominant parkinsonism, as well as disproportionately prominent postural instability. Gait analysis showed increased gait variability, reduced velocity and shortened step length bilaterally. Motor and gait abnormalities did not change after administration of levodopa. Her symptoms have remained stable for up to 52 months since symptom onset. We postulate that the infarction affecting the right putamen and claustrum could have led to a higher-level gait disorder mimicking NPH.
Assuntos
Claustrum , Hidrocefalia de Pressão Normal , Putamen , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Feminino , Putamen/diagnóstico por imagem , Putamen/irrigação sanguínea , Diagnóstico Diferencial , Idoso , Claustrum/diagnóstico por imagem , Derivação Ventriculoperitoneal , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/diagnóstico , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/diagnóstico , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH). METHODS: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aß42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders. Associations between biomarkers, diagnoses, and imaging were assessed by χ2, analysis of covariance, and linear regression methods. RESULTS: Median age at time of testing was 67 years (range, 19 to 96 years), median symptom duration was 2 years (range, 0.4 to 28 years), and median Short Test of Mental Status score was 30 (range, 0 to 38). Clinical diagnoses significantly correlated with different CSF biomarker values (χ2=208.3; P=10e-4). p-Tau181/Aß42 ratios above 0.023 positively correlated with Alzheimer dementia (more than individual measures). This ratio also had the best performance for differentiating Alzheimer dementia from NPH (area under the curve, 0.869). Imaging markers supportive of CSF dynamics disorders correlated with low Aß42, p-Tau181, and total-Tau. CONCLUSION: In a heterogeneous clinical population, abnormal p-Tau181/Aß42 ratios (>0.023) have the strongest association with Alzheimer dementia and probably represent a comorbid AD pathologic component in persons clearly matching non-AD neurodegenerative syndromes. Altered CSF dynamics were associated with lower concentrations of AD CSF biomarkers regardless of clinical diagnosis, but the ratio compensates for these changes. In the appropriate clinical setting, an isolated abnormal Aß42 should prompt consideration of NPH.