Idiopathic normal pressure hydrocephalus (iNPH) is a significant cause of the severe cognitive decline in the elderly population. There is no cure for iNPH, but cognitive symptoms can be partially alleviated through cerebrospinal fluid (CSF) diversion. In the early stages of iNPH, cognitive deficits occur primarily in the executive functions and working memory supported by frontostriatal circuits. As the disease progresses, cognition declines continuously and globally, leading to poor quality of life and daily functioning. In this review, we present recent advances in understanding the neurobiological mechanisms of cognitive impairment in iNPH, focusing on (1) abnormal CSF dynamics, (2) dysfunction of frontostriatal and entorhinal-hippocampal circuits and the default mode network, (3) abnormal neuromodulation, and (4) the presence of amyloid-β and tau pathologies.
Aged ; Cognitive Dysfunction/etiology* ; Humans ; Hydrocephalus, Normal Pressure/diagnosis* ; Peptide Fragments ; Quality of Life ; tau Proteins

BACKGROUND: Normal pressure hydrocephalus (NPH) is an etiology of dementia that is reversible following cerebrospinal fluid shunt placement, however, surgical intervention not always clinically effective and the respons to shunt therapy is poorly understood. Furthermore, NPH is a source of comorbidity in diseases with neurodegenerative pathology, such as Alzheimer's disease (AD). CASE REPORT: A 61-year-old woman presented to the neurology clinic with progressive gait difficulties and cognitive impairment over five years. Nine years after ventriculoperitoneal (VP) shunt treatment, the patient began to experience frequent falls. There was no improvement in clinical symptoms after the alteration of valve pressure on the VP shunt. An 18F-florbetaben amyloid positron emission tomography scan showed increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex. CONCLUSIONS: The patient of NPH was unresponsive to shunt therapy due to the development of AD.
Accidental Falls ; Alzheimer Disease* ; Amyloid ; Cerebrospinal Fluid Shunts ; Cognition Disorders ; Comorbidity ; Dementia ; Diffusion ; Female ; Gait ; Gyrus Cinguli ; Humans ; Hydrocephalus* ; Hydrocephalus, Normal Pressure ; Middle Aged ; Neurology ; Parietal Lobe ; Pathology ; Positron-Emission Tomography

A 68-year-old man presented with progressive impairment of gait, balance, and memory. He exhibited a slow and unstable gait. Formal neuropsychological evaluation showed a deficit in visuospatial function and memory with frontal dysfunctions. He was diagnosed as idiopathic normal pressure hydrocephalus with an Evans' ratio of 0.35. Four-and-a-half years after ventriculoperitoneal shunt placement, he showed a marked improvement in gait, as well as in visuospatial and frontal lobe functions. He benefited from shunt surgery for at least four-and-a-half years.
Aged ; Follow-Up Studies ; Frontal Lobe ; Gait ; Humans ; Hydrocephalus ; Hydrocephalus, Normal Pressure ; Memory ; Ventriculoperitoneal Shunt

BACKGROUND: Normal pressure hydrocephalus (NPH) is a poorly understood condition, which typically presents with the triad of gait disturbance, urinary incontinence and cognitive decline. Diagnosis of NPH is often challenging due to its varied presentation and overlap with other neurodegenerative diseases including multiple system atrophy (MSA). CASE REPORT: A 68-year-old male developed rapidly progressive gait difficulty, urinary incontinence and memory impairment. Neurologic examination showed parkinsonism affecting the right side and impaired postural reflexes. Brain MRI showed enlargement of the ventricles and narrowing of the high convexity cerebrospinal fluid (CSF) spaces with relative dilated Sylvian fissure, the supporting features of NPH. 18F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) PET showed decreased FP-CIT binding in the left posterior putamen and ¹⁸F-fluorodeoxyglucose PET showed decreased metabolism in the left basal ganglia, consistent with findings of MSA. CSF removal was performed and the symptoms were improved. The patient underwent ventriculo-peritoneal shunt and his gait and cognition improved. CONCLUSIONS: NPH is a potentially treatable neurological disorder. Therefore, it is necessary to consider the possibility of accompanying NPH when hydrocephalus is present in other neurodegenerative diseases.
Aged ; Basal Ganglia ; Brain ; Cerebrospinal Fluid ; Cognition ; Diagnosis ; Gait ; Humans ; Hydrocephalus* ; Hydrocephalus, Normal Pressure ; Magnetic Resonance Imaging ; Male ; Memory ; Metabolism ; Multiple System Atrophy* ; Nervous System Diseases ; Neurodegenerative Diseases ; Neurologic Examination ; Parkinsonian Disorders ; Putamen ; Reflex ; Urinary Incontinence ; Ventriculoperitoneal Shunt

BACKGROUND AND PURPOSE: Our aims were to analyze the characteristics of parkinsonian features and to characterize changes in parkinsonian motor symptoms before and after the cerebrospinal fluid tap test (CSFTT) in idiopathic normal-pressure hydrocephalus (INPH) patients. METHODS: INPH subjects were selected in consecutive order from a prospectively enrolled INPH registry. Fifty-five INPH patients (37 males) having a positive response to the CSFTT constituted the final sample for analysis. The mean age was 73.7±4.7 years. The pre-tap mean Unified Parkinson's Disease Rating Scale motor (UPDRS-III) score was 24.5±10.2. RESULTS: There was no significant difference between the upper and lower body UPDRS-III scores (p=0.174). The parkinsonian signs were asymmetrical in 32 of 55 patients (58.2%). At baseline, the Timed Up and Go Test and 10-meter walking test scores were positively correlated with the total motor score, global bradykinesia score, global rigidity score, upper body score, lower body score, and postural instability/gait difficulties score of UPDRS-III. After the CSFTT, the total motor score, global bradykinesia score, upper body score, and lower body score of UPDRS-III significantly improved (p<0.01). There was a significant decrease in the number of patients with asymmetric parkinsonism (p<0.05). CONCLUSIONS: In the differential diagnosis of elderly patients presenting with asymmetric and upper body parkinsonism, we need to consider a diagnosis of INPH. The association between gait function and parkinsonism severity suggests the involvement of similar circuits producing gait and parkinsonian symptoms in INPH.
Aged ; Cerebrospinal Fluid ; Diagnosis ; Diagnosis, Differential ; Gait ; Humans ; Hydrocephalus* ; Hydrocephalus, Normal Pressure ; Hypokinesia ; Parkinson Disease ; Parkinsonian Disorders* ; Prospective Studies ; Walking

OBJECTIVE: Normal pressure hydrocephalus (NPH) is a syndrome characterized by gait disturbance, memory impairment and urinary incontinence. The isotope cisternography (ICG) became less useful because of low accuracy and complications. We tried to evaluate the safety and value of the ICG. METHODS: We retrospectively collected data on ICG of 175 consecutive patients with a suspected hydrocephalus. We classified the ICG into four types by the ventricular reflux and circulation time. The ventricular size was measured by Evans index and the width of the third ventricle. RESULTS: There were three complications including one case of paraplegia. Type 4 was the most common type, observed in 53%. Type 3 (33%), type 2 (7%), and type 1 (7%) were observed less often. Type 4 was more common in patients with large ventricles. Types of the ICG were not related to the causes of hydrocephalus, gender, or age of the patients. Shunting was more frequently performed in type 4 (71%), compared to type 1 (17%), type 2 (33%), and type 3 (46%). Surgery was more common when the cause was vascular. After the shunt surgery, 33.0% were graded as the improved. Although there were some improvements even in the not-improved patients, they still needed many helps. The improvement was related to the preoperative state. CONCLUSION: ICG may bring a serious complication, however the incidence is very low. Although the predictability of response rate on the shunting is doubtful, ICG is a cheap and useful tool to select surgical candidates in NPH.
Diagnosis ; Gait ; Humans ; Hydrocephalus* ; Hydrocephalus, Normal Pressure ; Incidence ; Malpractice ; Memory ; Meningitis, Aseptic ; Paraplegia ; Radionuclide Imaging ; Retrospective Studies ; Third Ventricle ; Urinary Incontinence

In addition to classical triad such as gait disturbance, urinary incontinence and dementia, parkinsonian extrapyramidal motor signs and neuropsychiatric symptoms can be observed in patients with normal pressure hydrocephalus (NPH). In our case, a 46 year old female patient showed extrapyramidal symptoms such as bradykinesia, rigidity and neuropsychiatric symptoms such as agitation, anxiety, restlessness and regressed behavior beside two(gait disturbance & urinary incontinence) symptoms of three classical triad. It was difficult to diagnose this patient as NPH from the beginning because of her relatively young age and previous psychiatric mediation history for controlling advanced anxiety and affective disorder. Antiparkinsonian agents and discontinuation of psychiatric medications did not work for this patient. Patient's brain computed tomographic finding showed enlarged ventricles. We suspected NPH and did empirical drainage of 30mL CSF. Finally, patient's pyramidal and neuropsychiatric symptoms as well as two of three classical triad of NPH were improved dramatically within several days. It is important to consider NPH as one of the differential diagnosis in patient with parkinsonian symptoms and various neuropsychiatric symptoms who did not respond to usual clinical management especially in case of ventricular enlargement in neuroimaging because of its treatable property by CSF shunt operation.
Antiparkinson Agents ; Anxiety* ; Bipolar Disorder* ; Brain ; Dementia ; Diagnosis, Differential ; Dihydroergotamine ; Drainage ; Female ; Gait* ; Humans ; Hydrocephalus, Normal Pressure* ; Hypokinesia* ; Mood Disorders ; Negotiating ; Neuroimaging ; Psychomotor Agitation ; Urinary Incontinence

Five patients with favorable outcomes after a shunt operation in normal pressure hydrocephalus were analyzed with the aim of identifying consistent findings in a lumbar puncture (LP) test. The cases commonly showed improvement in at least one cognition and two gait LP parameters. We suggest that when judging the effects of LP on a shunt operation, the gait parameters need to be tailored to the gait status and the analyzed LP parameters should be evaluated at least twice at different times.
Cognition ; Gait ; Humans ; Hydrocephalus, Normal Pressure* ; Prognosis* ; Spinal Puncture*

Marchiafava-Bignami disease (MBD) is a rare disorder of demyelination or necrosis of the corpus callosum. Mainly, MBD is associated with alcohol and malnutrition. We report a 60-year-old woman with no history of alcohol consumption or malnutrition who had MBD as a possible complication of normal pressure hydrocephalus (NPH). The patient presented with a 2-month history of progressive gait unsteadiness, urinary incontinence, and forgetfulness, for which the patient underwent ventriculoperitoneal shunt surgery with remarkable improvement. Magnetic resonance imaging (MRI) demonstrated hyperintensity in the body and splenium of corpus callosum when she was brought to the hospital again with rapid deterioration of her mental ststus. It might be postulated that cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF-alpha) might have contributed to the development of MBD although not measured in this patient, given that TNF-alpha, as a proinflammatory cytokine mediating demyelinating process have been found in be increased in the CSF of NPH.
Alcohol Drinking ; Cerebrospinal Fluid ; Corpus Callosum ; Demyelinating Diseases ; Female ; Gait ; Humans ; Hydrocephalus, Normal Pressure* ; Magnetic Resonance Imaging ; Malnutrition ; Marchiafava-Bignami Disease* ; Middle Aged ; Necrosis ; Negotiating ; Tumor Necrosis Factor-alpha ; Urinary Incontinence ; Ventriculoperitoneal Shunt

OBJECTIVEThe management of secondary normal pressure hydrocephalus (sNPH) is controversial. Many factors may affect the surgery effect. The purpose of this study was to identify the possible factors influencing prognosis and provide theoretical basis for clinical treatment of sNPH.

METHODSA retrospective study was carried out to investigate the results of 31 patients with sNPH who underwent ventriculoperitoneal shunt surgery from January 2007 to December 2011. We processed the potential influencing factors by univariate analysis and the result further by multivariate logistic regression analysis.

RESULTSFactors including age, disease duration and Glasgow coma scale (GCS) score before surgery significantly influenced the prognosis of sNPH (P less than 0.05). Further logistic regression analysis showed that all the three factors are independent influencing factors.

CONCLUSIONAge, disease duration and GCS score before surgery have positive predictive value in estimating favorable response to surgical treatment for sNPH.

Adult ; Female ; Humans ; Hydrocephalus, Normal Pressure ; surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Ventriculoperitoneal Shunt