Shunt-responsive parkinsonism and reversible white matter lesions in patients with idiopathic NPH

Background   Idiopathic normal pressure hydrocephalus (iNPH) is a potentially treatable dementia and gait disorder with abnormal CSF dynamics. Objective   To investigate and characterize the changes in motor symptoms and CT and MRI features of iNPH before and after a shunt operation using specific evaluation criteria. Methods   We studied 17 definitive iNPH patients, diagnosed according to the clinical guidelines of both the Japanese Society of NPH and the International NPH Consultant Group, with ventricular enlargement (Evan’s index > 0.3) and narrowed CSF spaces at the high convexity on CT scan and /or MRI. The pre- and post-operative evaluation criteria for the gait and motor disturbances included the Japanese NPH Grading Scale-Revised (JNPHGSR), the Timed “Up and Go” test and the motor sections of the Unified Parkinson Disease Rating Scale. For cognitive impairments, the JNPHGSR, Mini Mental State Examination, Frontal Assessment Battery and Trail Making Test were used. White matter lesions were rated from the CT and/or MRI using a validated visual rating scale. Results   All patients showed specific CT and MRI findings, consisting of diffusely-dilated Sylvian fissure, as well as narrowed CSF space at the high convexity. Fifteen patients (88 %) showed white matter lesions on their CT or MRI images. These signs were ameliorated in all patients after the shunt operation. Evan’s index and the mean total scores on the visual scale for white matter lesions also improved significantly. Clinically, the patients had frequent parkinsonism (71 %), but relatively few had a history of either small-vessel diseases (29 %), hypertension (41 %) or diabetes (35 %). All patients showed gait disturbances, and these symptoms, including postural instability and body bradykinesia, improved significantly after the operation. Over half also showed signs of cognitive impairment and urinary incontinence, and all such symptoms and signs improved significantly. Conclusion   iNPH often appears as a shunt-responsive type of parkinsonism and reversible white matter lesions among the geriatric population.     

Differences in Brain Morphology between Hydrocephalus Ex Vacuo and Idiopathic Normal Pressure Hydrocephalus

ObjectiveThe distinction between idiopathic normal pressure hydrocephalus (iNPH) and hydrocephalus ex vacuo caused by encephalic volume loss remains to be established. This study aims to investigate radiological parameters as clinically useful tools to discriminate iNPH from hydrocephalus ex vacuo caused by Alzheimer’s disease (AD). MethodsA total of 54 patients with ventriculomegaly (iNPH, 25; hydrocephalus ex vacuo, 29) were recruited in this study. Consequently, nine radiological parameters were compared between iNPH and hydrocephalus ex vacuo using magnetic resonance imaging (MRI). ResultsA small callosal angle (CA), the Sylvian fissure dilatation, and absence of narrowing of superior parietal sulci discriminated the iNPH group from the hydrocephalus ex vacuo group (p<0.05). The final binary logistic regression model included narrowing of superior parietal sulci, degrees of the CA, and height of the Sylvian fissure after controlling for age and global Clinical Dementia Rating (CDR). The composite score made from these three indicators (narrowing of superior parietal sulci, degrees of the CA, and height of the Sylvian fissure) was statistically different between iNPH and hydrocephalus ex vacuo. ConclusionThe narrowing of the CA, dilatation of the Sylvain fissure, and narrowing of superior parietal sulci may be used as radiological key indices and noninvasive tools for the differential diagnosis of iNPH from hydrocephalus ex vacuo.     

Idiopathischer Normaldruckhydrozephalus

AIM: The measurement of CSF flow in the aqueduct has been a focus of interest since the development of MR imaging (MRI) techniques for this purpose in diagnosing idiopathic normal-pressure hydrocephalus (iNPH).The purpose of this prospective study was to determine the ability of this diagnostic tool to replace invasive methods in establishing the diagnosis of iNPH. PATIENTS AND METHODS: Between January 2003 and April 2005, 61 patients with the Hakim triad of clinical symptoms and dilated ventricular systems underwent the intrathecal infusion test, cerebrospinal tap test, and phase-contrast MRI to measure CSF flow rate in the aqueduct. Shunted patients were controlled 12 months postoperatively. Pre- and postoperative clinical symptoms were evaluated with the Kiefer score. Outcome was calculated according to the NPH recovery rate. RESULTS: According to these criteria the patients were classified into groups of 41 with iNPH and 20 with brain atrophy. Of the iNPH patients, 39 were shunted and two did not agree to surgery. The mean Kiefer score of the shunted patients was statistically significantly lower after surgery. The aqueductal CSF flow rate of these patients was statistically analyzed and showed that a flow rate of more than 24.5 ml/min is 95% specific to iNPH. CONCLUSIONS: Measurement of the CSF flow rate in the aqueduct using phase-contrast MRI is a highly specific preselective method for diagnosing iNPH.     

Asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on MRI (AVIM) in the elderly: a prospective study in a Japanese population

We investigated if there are individuals at a preclinical stage of idiopathic normal pressure hydrocephalus (iNPH) in a general population. All the residents (n=1142) aged 61 years (n=306, men/women=156/150) and 70-72 years (n=836, men/women=356/480) in the two communities of Japan were requested to take brain MRI examination. The "iNPH features on MRI" were defined as an Evans index of >0.3 and a narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum. "Possible iNPH" was defined as the presence of one or more symptoms of iNPH, together with such MRI features. 790 (69.2%) of the 1142 residents participated in this study. Among them, 51 individuals (men/women=35/16) (6.46%) had the enlarged ventricles (Evans index of >0.3), 12 (men/women=7/5) (1.52%) of which showed the iNPH features on MRI. Of the 12 individuals, 8 (men/women=4/4) (1.01%) were asymptomatic, while 4 (men/woman=3/1) (0.51%) had gait disturbance and/or dementia (possible iNPH). During a follow-up period of 4-8 years, two of the 8 asymptomatic subjects developed dementia and/or gait disturbance with worsening of ventriculomegaly on brain MRI in one case. The prevalence of possible iNPH was 0.51% (4/790) among Japanese elderly (>61 years of age). Asymptomatic ventriculomegaly with the iNPH features on MRI (AVIM) may represent a preclinical stage of iNPH.     

Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test

Idiopathic Normal Pressure Hydrocephalus (iNPH)—the leading cause of reversible dementia in aging—is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH‐specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer''s disease (AD). Here we investigate the resting‐state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer''s pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive‐control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD‐pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross‐network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.     

Enterovirus 71 meningoencephalitis complicating rituximab therapy

Normal pressure hydrocephalus (NPH) has two clinical forms: secondary NPH and idiopathic NPH (iNPH). Most patients with NPH occur sporadically: until now, only two families have been reported to have sibling cases of NPH. We here report a large family with 4 patients with elderly-onset NPH in three generations. All of them had cognitive impairment, gait disturbance, and urinary problems, along with normal pressure of cerebrospinal fluid. Their brain MRI showed enlargement of the ventricles and a disproportional narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum, which are the features of iNPH on MRI. The family interview also disclosed additional 4 patients who were suspected as having NPH. The disease seems to be inherited in an autosomal-dominant fashion. No known causes of secondary NPH were found in any of the patients. This is the first report to show a large family with NPH patients in three generations, who had clinical and MRI features indistinguishable from iNPH. This seems to represent a novel subgroup of NPH, familial NPH.     

Non-invasive vagus nerve stimulation significantly improves quality of life in patients with persistent postural-perceptual dizziness

Amyloid positron emission tomography ([18F] florbetaben (FBB) PET) can be used to determine concomitant Alzheimer’s disease (AD) in idiopathic normal pressure hydrocephalus (iNPH) patients. FBB PET scans and the tap test were performed in 31 patients with clinically suspected iNPH, and amyloid positive (iNPH/FBB+) and negative (iNPH/FBB?) groups were compared with respect to clinical characteristics. We evaluated prognostic value of FBB PET scans by analyzing the response to the tap test using a linear mixed model. We also performed a multivariable regression analysis to investigate whether amyloid PET positivity can predict the positive tap test response independent of other AD biomarkers. The results showed that the iNPH/FBB+ group (7/31, 22.6%) had a higher percentage of APOE4 carriers, lower Aβ42, higher CSF t-tau, and p-tau/Aβ42 ratio than the iNPH/FBB? group (24/31, 77.4%), while the two groups did not differ in imaging characteristics. The iNPH/FBB? group had a higher percentage of tap responders and showed a greater improvement in gait scores after the tap test than the iNPH/FBB+ group (group-tap test effect interaction, p = 0.035). A multivariable logistic regression analysis showed that amyloid positivity on PET scans (OR 0.03, p = 0.029) and CSF p-tau (OR 0.87, p = 0.044) were independently associated with the positive tap test response. Among 21 tap responders in the iNPH/FBB? group, 14 patients received shunt surgery and 12/14 (85.7%) patients showed symptom improvement. Our findings suggest that amyloid PET scans can help determine which iNPH patients will benefit from shunt surgery by discriminating concomitant AD.     

Analysis of Empty Sella Secondary to the Brain Tumors

Objective

The definition of empty sella syndrome is ''an anatomical entity in which the pituitary fossa is partially or completely filled with cerebrospinal fluid, while the pituitary gland is compressed against the posterior rim of the fossa''. Reports of this entities relating to the brain tumors not situated in the pituitary fossa, have rarely been reported.

Methods

In order to analyze the incidence and relationship of empty sella in patients having brain tumors, the authors reviewed preoperative magnetic resonance imaging (MRI) of 72 patients with brain tumor regardless of pathology except the pituitary tumors. The patients were operated in single institute by one surgeon. There were 25 males and 47 females and mean patient age was 53 years old (range from 5 years to 84 years). Tumor volume was ranged from 2 cc to 238 cc.

Results

The overall incidence of empty sella was positive in 57/72 cases (79.2%). Sorted by the pathology, empty sella was highest in meningioma (88.9%, p = 0.042). The empty sella was correlated with patient''s increasing age (p = 0.003) and increasing tumor volume (p = 0.016).

Conclusion

Careful review of brain MRI with periodic follow up is necessary for the detection of secondary empty sella in patients with brain tumors. In patients with confirmed empty sella, follow up is mandatory for the management of hypopituitarism, cerebrospinal fluid (CSF) rhinorrhea, visual disturbance and increased intracranial pressure.     

Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal

Pseudo-continuous arterial spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.     

Two elderly patients with idiopathic normal pressure hydrocephalus diagnosed by head MRI and tap test

Dementia, gait disturbance and urinary incontinence were noted in two elderly patients, and diagnosed as idiopathic normal pressure hydrocephalus (iNPH). Case 1 was a 79‐year‐old man in whom dementia symptoms appeared 2 years ago. Gait disturbance and urge incontinence of urine developed later, and the patient visited our hospital. Walking was wide‐based and frozen gait was noted at the time of visiting our hospital. The mini‐mental state examination (MMSE) score was 11. A head MRI detected expansion of the cerebral ventricles and sylvian fissures, and narrowing of the cerebral fissures and the subarachnoid space in the higher convexity region. The diagnosis of iNPH was made based on the clinical symptoms and imaging findings, and a shunt operation (cerebrospinal fluid shunt) was performed in the neurosurgery department. Gait disturbance and cognitive function slightly improved after the operation. Case 2 was an 81‐year‐old woman who had had brachybasia for 1 year, and swayed from side to side while walking. Since disorientation and urge incontinence transiently occurred, the patient visited our hospital. The MMSE score was 24. Head MRI findings were similar to those in case 1. The cerebrospinal tap test was performed, and walking improved in the 1‐week course observation. iNPH is not very well recognized, compared to secondary NPH, and is likely to be overlooked because differentiation from Alzheimer's disease and vascular dementia based on symptoms and imaging is difficult in elderly patients. As iNPH is treatable by accurate diagnosis and therapy, the accumulation of cases indicated for shunt operation may be necessary.     

Oligoclonal bands and MRI in clinically isolated syndromes: predicting conversion time to multiple sclerosis

The objective of the study was to evaluate whether the presence of oligoclonal bands (OB) adds information in predicting CIS conversion to clinical definite multiple sclerosis (CDMS) and conversion time to CDMS. From 1998 to 2006, CIS patients were included in a prospective study. Patients underwent brain MRI and OB determination within 2 months of the first demyelinating event. We analyzed conversion to CDMS and time to conversion to CDMS according to abnormal MRI and the presence of OB. Forty patients were included. Fifteen patients (37%) converted to CDMS; 14 of them (93.3%) had abnormal baseline MRI (P = 0.01, RR = 5.9; 95% CI 1.3–10.1) and 13 (86.7%) had positive OB in CSF (P = <0.01, RR = 5.3; 95% CI 1.6–9.5). The risk of conversion to CDMS in patients with positive OB and abnormal baseline MRI was significantly higher compared to patients negative for both tests or with only one positive (RR = 9.1; 95% CI 3.5–14.6). Time to conversion to CDMS was 6.8 ± 3.5 months for patients with OB and abnormal baseline MRI and 19 ± 14 months for patients with only one abnormal test. CIS patients with abnormal baseline OB in CSF have a higher risk for developing CDMS. Regarding conversion time to CDMS, when abnormal MRI was added to positive OB, patients converted faster (mean time, 6 vs. 19 months). This information may be useful when considering treatment in CIS patients.     

Idiopathic normal-pressure hydrocephalus,cerebrospinal fluid biomarkers,and the cerebrospinal fluid tap test

Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid β-42 (Aβ-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer’s disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers Aβ-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF Aβ-42 correlated with poor cognitive performance (r = 0.687, p < 0.001 for Korean Mini Mental State Examination; r = 0.568, p = 0.001 for Frontal Assessment Battery; r = −0.439, p = 0.014 for iNPH grading scale [iNPHGS] cognitive score; r = −0.588, p = 0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r = −0.624, p < 0.001 for Timed Up and Go Test; r = −0.652, p < 0.001 for 10 meter walking test; r = −0.578, p = 0.001 for Gait Status Scale; r = −0.543, p = 0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/Aβ-42 ratios were significantly higher in CSFTT non-responders compared to responders (p = 0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses.     

Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a subtype of dementia that may be successfully treated with cerebrospinal fluid (CSF) diversion. Recently, magnetic resonance imaging (MRI) using a MRI contrast agent as a CSF tracer revealed impaired clearance of the CSF tracer from various brain regions such as the entorhinal cortex of iNPH patients. Hampered clearance of waste solutes, for example, soluble amyloid-β, may underlie neurodegeneration and dementia in iNPH. The goal of the present study was to explore whether iNPH is associated with altered subcellular distribution of aquaporin-4 (AQP4) water channels, which is reported to facilitate CSF circulation and paravascular glymphatic drainage of metabolites from the brain parenchyma. Cortical brain biopsies of 30 iNPH patients and 12 reference individuals were subjected to AQP4 immunogold cytochemistry. Electron microscopy revealed significantly reduced density of AQP4 water channels in astrocytic endfoot membranes along cortical microvessels in patients with iNPH versus reference subjects. There was a significant positive correlation between density of AQP4 toward endothelial cells (perivascular) and toward parenchyma, but the reduced density of AQP4 toward parenchyma was not significant in iNPH. We conclude that perivascular AQP4 expression is attenuated in iNPH, potentially contributing to impaired glymphatic circulation, and waste clearance, and subsequent neurodegeneration. Hence, restoring normal perivascular AQP4 distribution may emerge as a novel treatment strategy for iNPH.     

Is the midbrain involved in the manifestation of gait disturbance in idiopathic normal-pressure hydrocephalus?

Gait disturbance is the most common symptom in idiopathic normal-pressure hydrocephalus (iNPH). However, its pathophysiology in iNPH has not been clarified. Some researchers have hypothesized that the mesencephalic locomotor region, which is a functionally defined area in the brainstem playing an important role in locomotion, is involved in the development of gait disturbance in iNPH. The purpose of the study was to investigate whether the midbrain is involved in the manifestation of gait disturbance in iNPH. Twenty-one iNPH patients who showed clinical improvements after shunt surgery were studied. Brain magnetic resonance imaging (MRI) was performed and clinical symptoms were assessed before and 1 year after surgery. Gait disturbance was assessed by the Timed Up and Go test and gait subcategory of the iNPH Grading Scale, a validated assessment tool for iNPH symptoms. Anteroposterior, left-to-right diameter and cross-sectional areas of the midbrain were measured at the inferior collicular level of axial images in MRI. The diameters and cross-sectional area of the midbrain at baseline did not show significant correlation with gait assessments at baseline (Spearman’s correlation). The midbrain measurement did not show significant difference between the baseline and postoperative values (paired t test), and its change rates did not show significant correlation with the change (rates) of the gait assessments. In this study there were no findings to suggest involvement of the midbrain in the manifestation of gait disturbance in iNPH. The hypothesis that the mesencephalic locomotor region is involved in the manifestation of gait disturbance in iNPH needs to be reconsidered.     

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus

Czosnyka Z, Owler B, Keong N, Santarius T, Baledent O, Pickard JD, Czosnyka M. Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.
Acta Neurol Scand: 2011: 123: 414–418.
© 2010 John Wiley & Sons A/S. Objective – Cerebrospinal fluid (CSF) pressure–volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)? Methods – We investigated 92 patients presenting with iNPH. Mean age was 73 (range 47–86). There were 60 men and 32 women. They all presented with gait disturbance and ventricular dilatation. Memory deficit occurred in 72% and urinary incontinence in 52% of patients. All patients underwent computerized CSF infusion tests. Sixty‐four shunted patients were available for follow‐up, and their improvement was expressed using the NPH score. Results – Mean intracranial pressure (ICP) was 10.1 ± 5.1 mmHg, and mean resistance to CSF outflow was 17.3 ± 5.2 mmHg/(ml/min). Mean duration of symptoms was 24 ± 19 months (range from 2 weeks to 86 months). Baseline ICP, magnitude of ICP pulse waveform, brain compliance and improvement after shunting (72% of patients improved) did not exhibit any dependency on the duration of symptoms. The resistance to CSF outflow showed a strong tendency to decrease in time with the duration of symptoms beyond 2 years (R = −0.702; P < 0.005). Conclusion – This is a preliminary observation, and it suggests that for patients with duration of symptoms longer than 2–3 years, the threshold for normal resistance to CSF outflow should be duration‐adjusted.     

Delayed cerebrospinal fluid rhinorrhea after gamma knife surgery in a patient with a growth hormone-secreting adenoma

We report a patient who developed delayed cerebrospinal fluid (CSF) rhinorrhea 11 years after gamma knife radiosurgery for a growth hormone (GH)-secreting adenoma. The treatment dose was 18 Gy for the tumor margin (50% isodose). One year later, an MRI of the head revealed that the tumor size had decreased. Eleven years later, the patient developed CSF rhinorrhea from the left nostril. Subsequent MRI examination revealed complete remission of the tumor in the sella turcica and the empty sella. The patient was admitted for direct endoscopic surgical repair of the skull base. We suggest that the cause of the CSF rhinorrhea is secondary empty sella. The other potential causes may be the original invasiveness of the tumor or delayed radiation damage to the mucous membranes of the skull. Long-term follow-up is required to monitor recurrence of CSF rhinorrhea.     

Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study.

The sylvian fissure is known to be one of the most asymmetric structures of the human brain. Sylvian fissure length was measured in post-mortem brains of 35 schizophrenic patients and 33 matched non psychiatric control subjects. The schizophrenics showed a significantly reduced length of the left sylvian fissure (-16%, p less than 0.0001) compared to the control subjects, while the right sylvian fissure length was unchanged. Sylvian fissure asymmetry (left/right ratio) was more reduced in male schizophrenics (-24%, p less than 0.001) than in female patients (-16%, p less than 0.03). This finding is consistent with several post-mortem and MRI studies showing left temporal lobe pathology in a significant proportion of patients and may indicate that schizophrenia is a disorder of early neurodevelopment causing impaired cerebral lateralization.     

特发性正常压力脑积水脑脊液标志物的变化

目的 探讨特发性正常压力脑积水（iNPH）病人脑脊液（CSF）磷酸化tau蛋白（p-tau）、总tau蛋白（t-tau）、转化生长因子-β1（TGF-β1）的变化。方法 前瞻性收集2018年6月至2020年2月经分流术临床确诊的16例iNPH为确诊组,同期行脑脊液释放试验无效的16例可疑iNPH为可疑组。采用酶联免疫吸附试验检测CSF中p-tau、t-tau、TGF-β1水平。结果 确诊组CSF中p-tau水平显著低于可疑组（P<0.01）,TGF-β1水平显著高于可疑组（P<0.01）。两组CSF中t-tau水平无统计学差异（P>0.05）。8例确诊iNPH术后7 d的CSF中p-tau、t-tau水平较术前均明显降低（P<0.05）,而TGF-β1水平与术前无统计学差异（P>0.05）。结论 本文结果提示CSF中p-tau、t-tau、TGF-β1在iNPH诊断、分流术效果评估中具有一定的作用。     

Primary central nervous system vasculitis and moyamoya disease: similarities and differences

Primary central nervous system vasculitis (PCNSV) and moyamoya disease (MMD) represent rare and poorly-understood causes of stroke. Both may present with similar clinical and auxiliary findings, but differentiation is extremely important because they require different treatment regimens. Our cohort included 21 white patients with PCNSV and 21 white patients with MMD. Clinical and diagnostic features were obtained by retrospective chart review; follow-up information and outcome were obtained prospectively. Data were compared between patients with PCNSV and MMD using Chi square test or Fisher’s exact test for categorical data and Mann–Whitney U test for continuous data. The mean age at symptom onset was 42.48 years in PCNSV and 31.0 years in MMD (p = 0.008). All patients with MMD presented with ischemic events while cerebral ischemia was observed in only 14 of 21 patients (66.7%) with PCNSV (p = 0.004). There was no significant difference regarding the frequency of headaches, which represented an important symptom in both conditions. Conventional cerebral angiography verified correct diagnosis in 13 of 17 patients (76.5%) with PCNSV while angiogram verified correct diagnosis in all patients with MMD (p = 0.032). MRI and cerebrospinal fluid studies were appropriate to differentiate between the inflammatory and the non-inflammatory disease. Three PCNSV patients and two MMD patients died within documented follow-up. Despite important pathophysiological and angiographic differences, PCNSV and MMD may present with similar clinical and auxiliary findings. An intensive workup including MRI, conventional cerebral angiography and CSF studies is required to avoid misdiagnosis.     

JNCL patients show marked brain volume alterations on longitudinal MRI in adolescence

Abstract   Juvenile neuronal ceroid lipofuscinosis (JNCL, CLN3) is an inherited lysosomal disease. We used longitudinal MRI, for the first time, to evaluate the rate of brain volume alterations in JNCL. Six patients (mean ages of 12.4 years and 17.3 years) and 12 healthy controls were studied twice with 1.5 T MRI. White matter (WM), gray matter (GM) and CSF volumes were measured from the sets of T1-weighted 3-dimensional MR images using a fully automated image-processing procedure. The brain volume alterations were calculated as percentage change per year. The GM and whole brain volumes decreased and the CSF volume increased significantly more in the patients than in controls (p-values for the null hypothesis of equal means were 0.001, 0.004, and 0.005, respectively). We found no difference in the WM volume change between the populations. In patients, the GM volume decreased 2.4 % (SD 0.5 %, p 0.0001 for the null hypothesis of zero mean change between observations), the whole brain volume decreased 1.1 % (SD 0.5 %, p = 0.003), and the CSF volume increased 2.7 % (SD 1.8 %, p = 0.01) per year. In normal controls, only the mean white matter volume was significantly altered (0.8 % increase, SD 0.7 %, and p = 0.001). Conclusion   We demonstrated by longitudinal MRI that the annual rate of the gray matter loss in adolescent JNCL patients is as high as 2.4 %.