Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming ...of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
Objectives
Comorbidities of idiopathic normal pressure hydrocephalus (iNPH), such as Alzheimer's disease (AD) and Parkinson's spectrum (PS) disorder, can affect the long‐term prognosis of ...cerebrospinal fluid (CSF) shunting. Therefore, it is important to be able to predict comorbidities in the early stage of the disease. This study aimed to predict the comorbidities of iNPH using neuropsychological tests and cognitive performance evaluation.
Materials & Methods
Forty‐nine patients with possible iNPH were divided into three groups: iNPH without AD or PS comorbidity (group‐1), iNPH with AD comorbidity (group‐2), and iNPH with PS comorbidity (group‐3), according to CSF biomarkers such as phosphorylated tau and dopamine transporter imaging. Scores on the new EU‐iNPH‐scale, which is based on 4 neuropsychological tests (Rey Auditory Verbal Learning Test, Grooved Pegboard test, Stroop colour‐naming test and interference test), were compared for each group. In addition, the scores before and 12 months after CSF shunting for each group were compared.
Results
EU‐iNPH‐scale using 4 neuropsychological tests could distinguish group‐1 from group‐2 or group‐3 by area under the curve values of 0.787 and 0.851, respectively. Patients in group‐1 showed a remarkable increase in memory and learning ability after surgery. Group‐2 performed significantly poorer than group‐1 patients on memory testing, but otherwise showed improvements in most of the neuropsychological tests. Group‐3 performed significantly worse than group‐1 patients—especially on Stroop tests—but showed post‐surgery improvement on only the Stroop colour‐naming test.
Conclusions
The 4 neuropsychological tests of the EU‐iNPH‐scale can help predict iNPH comorbidities and evaluate the prognosis of CSF shunting.
Disproportionately Enlarged Subarachnoid space Hydrocephalus (DESH) is considered as an important imaging feature of idiopathic normal pressure hydrocephalus (iNPH).
Subjects aged 60 and over in a ...memory clinic and a community-based cohort were assessed for the presence of ventriculomegaly, Sylvian dilatation, and high convexity tightness by neuroimaging, and a clinical triad of iNPH symptoms, i.e. cognitive, gait and urinary symptoms.
In the memory clinic-based study (548 subjects), the prevalence of DESH was 1.1% and increased with age. The clinical triad was significantly more frequent in subjects with DESH (50%) compared to those with normal images (none), Sylvian dilatation (7%), and ventriculomegaly (12%). Gait disturbance was also significantly more frequent in DESH (83%) compared to those with normal images (2%), Sylvian dilatation (14%), and ventriculomegaly (26%). In the community-based cohort (946 subjects), the prevalence of DESH was 1.0% and increased with age. The clinical triad (11%) was significantly more common in subjects with DESH compared to those with normal images (none), Sylvian dilatation (2%), and ventriculomegaly (7%). Gait disturbance was also significantly more common in DESH (33%) compared to those with normal images (1%), Sylvian dilatation (4%), and ventriculomegaly (10%).
The reported prevalence of DESH was approximately 1%, and increased with age. DESH and high convexity tightness were specifically associated with the clinical triad of iNPH. Of the triad, gait disturbance was associated to DESH and high convexity tightness.
•Prevalence of DESH in a memory clinic-based cohort was 1.1% and increased with age.•Prevalence of DESH in a community-based cohort was 1.0% and increased with age.•Presence of high convexity tightness is a highly predictive feature of DESH.•Gait disturbance seemed to be the most specific symptom to DESH.•Prevalence of DESH in subjects with dementia was 2.2% in the memory clinic and 6.5% in the community-based cohort.
Intracranial hypotension is a disorder characterized by low cerebrospinal fluid (CSF) pressure typically caused by loss of CSF. Although some mechanisms account for the CSF leakage have been ...elucidated, spinal canal stenosis has never been reported as a pathological cause of intracranial hypotension. C1-C2 sign is a characteristic imaging feature, which indicates CSF collection between the spinous processes of C1 and C2, occasionally observed on magnetic resonance imaging (MRI) in patients with intracranial hypotension.
A 58-year-old man was presented to our institute with complaints of posterior cervical pain persisting for 3 months, along with numbness and muscle weakness of extremities. A fat suppression T2-weighted image of MRI illustrated fluid collection in the retrospinal region at C1-C2 level, and an 111In-DTPA cisternoscintigram clearly revealed the presence of CSF leakage into the same region. The MRI also showed stenosis in spinal canal at C3/4 level, and a computed tomography (CT) myelogram suggested a blockage at the same level. We gave a diagnosis as intracranial hypotension due to the CSF leakage, which might be caused by the spinal canal stenosis at C3/4 level. Despite 72 h of conservative therapy, a brain CT showed the development of bilateral subdural hematomas. We, therefore, performed burr-hole drainage of the subdural hematoma, blood-patch therapy at C1/2 level, and laminoplasty at C3-4 at the same time. Improvement of symptoms and imaging features which suggested the CSF leak and subdural hematoma were obtained post-operatively.
The present case suggested the mechanism where the CSF leakage was revealed as fluid collection in the retrospinal region at C1-C2 level. Increased intradural pressure due to the spinal canal stenosis resulted in dural tear. CSF leaked into the epidural space and subsequently to the retrospinal region at C1-C2 level, due to the presence of spinal canal stenosis caudally as well as the vulnerability of the tissue structure in the retrospinal region at C1-C2 level. Thus, our theory supports the mechanisms of previously reported CSF dynamics associated to C1-C2 sign, and also, we suggest spinal canal stenosis as a novel etiology of intracranial hypotension.
Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential ...genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus.
Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus.
CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20
) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks.
This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20
mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.
Idiopathic normal pressure hydrocephalus (iNPH) is a condition resulting from impaired cerebrospinal fluid (CSF) absorption and excretion characterized by a triad of symptoms comprising dementia, ...gait disturbance (impaired trunk balance), and urinary incontinence. CSF biomarkers not only assist in diagnosis but are also important for analyzing the pathology and understanding appropriate treatment indications. As the neuropathological findings characteristic of iNPH have yet to be defined, there remains no method to diagnose iNPH with 100% sensitivity and specificity. Neurotoxic proteins are assumed to be involved in the neurological symptoms of iNPH, particularly the appearance of cognitive impairment. The symptoms of iNPH can be reversed by improving CSF turnover through shunting. However, early diagnosis is essential as once neurodegeneration has progressed, pathological changes become irreversible and symptom improvement is minimal, even after shunting. Combining a variety of diagnostic methods may lead to a more definitive diagnosis and accurate prediction of the prognosis following shunt treatment. Identifying comorbidities in iNPH using CSF biomarkers does not contraindicate shunting-based intervention, but does limit the improvement in symptoms it yields, and provides vital information for predicting post-treatment prognosis.
The aim of this study was to evaluate the water diffusivity changes along the perivascular space after lumboperitoneal shunt (LPS) surgery in idiopathic normal pressure hydrocephalus.
Nine patients ...diagnosed with idiopathic normal pressure hydrocephalus (iNPH; three men and six women, mean age ± SD = 75.22 ± 5.12 years) according to the guidelines for iNPH in Japan were included in the study. Post-LPS surgery, six patients with iNPH who exhibited improvement in symptoms were defined as responder subjects, while three patients with iNPH who did not were defined as non-responder subjects. We calculated the mean analysis along the perivascular space (ALPS) index of the left and right hemispheres and compared the differences between pre- and post-LPS surgery mean ALPS indices in iNPH patients. In the responder or non-responder subjects, the mean ALPS indices in the pre- and post-operative iNPH groups were compared using Wilcoxon signed-rank tests. Next, correlation analyses between pre- and post-operation changes in the mean ALPS index and clinical characteristics were conducted.
The mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (
= 0.021). In responder subjects, the mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (
= 0.046). On the other hand, in the non-responder subjects, the mean ALPS index of the post-operative iNPH group was not significantly different compared to the pre-operative iNPH group (
= 0.285). The mean ALPS index change was not significantly correlated with changes in the Mini-Mental State Examination (MMSE) score (
= -0.218,
= 0.574), Frontal Assessment Battery (FAB) score (
= 0.185,
= 0.634), Trail Making Test A (TMTA) score (
= 0.250,
= 0.516), and Evans' index (
= 0.109,
= 0.780). In responder subjects, the mean ALPS index change was significantly correlated with Evans' index in pre-operative patients with iNPH (
= 0.841,
= 0.036).
This study demonstrates the improved water diffusivity along perivascular space in patients with iNPH after LPS surgery. This could be indicative of glymphatic function recovery following LPS surgery.
We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG ...expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls. Field excitatory postsynaptic potentials declined with age in LRG-Tg compared with controls at 8, 24, and 48 weeks. Paired-pulse ratio decreased with age in LRG-Tg, while increased in controls. As a result, long-term potentiation was retained in 8- and 24-week-old LRG-Tg, whereas diminished in 48-week-old LRG-Tg compared with age-matched controls. Electron microscopy observations revealed fewer synaptic vesicles and junctions in LRG-Tg compared with age-matched controls, which became significant with age. Hippocampal LRG overexpression contributes to synaptic dysfunction, which leads to memory impairment with advance of age.
Experiencing a ventriculoperitoneal (VP) shunt complication is a major obstacle in the management of hydrocephalus. Degradation of a shunt catheter associated with surrounding tissue calcification ...could be 1 reason for a difference in facture rates. Furthermore, tissue reactions around cerebrospinal fluid shunts may be a sign of bacterial shunt infection, which is not uncommon.
A 31-year-old man was living with a ventriculoperitoneal shunt since childhood. Consequently, his cerebrospinal fluid absorption was supposed to be modified by the shunt. Shunt malfunction later occurred concomitant with symptoms of headache and repeated vomiting. He had undergone shunt revision a year before presentation, but examination revealed that a new, extremely rare calcified lesion had formed in the aponeurosis of the abdomen, compressing the shunt tube. We removed it and replaced the shunt tube, thus relieving his symptoms.
We treated a rare case of shunt dysfunction caused by calcification of the aponeurosis coinciding with significant weight gain over the course of a year. To the best of our knowledge, this is the first report to describe a case of shunt malfunction caused by calcification of the aponeurosis.
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