White matter changes in normal pressure hydrocephalus and Binswanger disease: specificity,predictive value and correlations to axonal degeneration and demyelination

OBJECTIVES: To analyse the diagnostic and prognostic value of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) magnetic resonance imaging (MRI) changes and their relation to symptoms and cerebrospinal fluid (CSF) markers of demyelination (sulphatide) and axonal degeneration [neurofilament triplet protein (NFL)] in a large series of patients with normal pressure hydrocephalus (NPH) and Binswanger disease (BD). MATERIALS AND METHODS: PVH and DWMH were determined by a semi-automatic segmentation method on T2-weighted images in 29 patients with NPH and 17 patients with BD. CSF analyses, psychometric testing and quantification of balance, gait and continence were performed in all patients and also postoperatively in NPH patients. RESULTS: No MRI variable could identify NPH or BD patients. Abundant PVH and DWMH preoperatively correlated with improvement in gait, balance and psychometric performance after shunt surgery (P < 0.05). CSF sulphatide correlated positively with the amount of DWMH (P < 0.05) while NFL was correlated to both PVH and DWMH (P < 0.05). Abundant PVH correlated with poor psychometric performance while DWMH correlated with gait disturbance (P < 0.05). Postoperative reduction in PVH correlated with improvement in gait, balance and psychometric performance. CONCLUSION: In spite of a refined quantification method, NPH and BD patients exhibited similar MRI changes. MRI had a predictive value in NPH patients. DWMH might relate to demyelination and PVH to neuronal axonal dysfunction. NPH and BD share the major part of symptoms and MRI changes, indicating a common pathophysiological pattern, and we raise the question of how to treat BD patients.     

Gait dysfunction in Parkinson’s disease and normal pressure hydrocephalus: a comparative study

Our objectives were to characterize gait dysfunction in Parkinson’s disease (PD) and normal pressure hydrocephalus (NPH) patients, in a comparative analysis. We used a walking test to determine gait velocity (GV), stride length (SL), stride cadence and the presence of frontal (FG) and sub-cortical hypokinetic gait (SHG) features. Equilibrium was tested with the shoulder tug test (STT). These variables were used in cluster analysis, to classify subjects according to gait dysfunction. PD patients were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY) scale. NPH patients were reassessed after high volume lumbar puncture (LP). NPH (n = 35) and PD (n = 40) patients had lower SL, GV and STT scores than controls (n = 30). NPH patients had worse results in SL, GV and STT than PD and a higher frequency of both FG and SHG features, compared to PD and the control groups. We found a severe/moderate gait dysfunction cluster, formed by 33 NPH patients and 11 PD patients, and a normal/mild dysfunction cluster, comprising 2 NPH, 29 PD patients and all control subjects. PD patients in the first cluster had worse UPDRS (except for tremor) and HY scores. In NPH patients, all gait variables improved after LP, although not to the controls level. PD and NPH gait was similarly characterized by loss of balance, slowness and small steps, although NPH patients performed worse. In PD patients, gait dysfunction comparable to that of NPH patients was associated with worse motor stage and the akinetic-rigid variant.     

Gait analysis in idiopathic normal pressure hydrocephalus--which parameters respond to the CSF tap test?

OBJECTIVES: Normal pressure hydrocephalus (NPH) is an often underestimated cause of hypokinetic gait disorders in the elderly. Diagnosing NPH is a complex problem, since many symptoms overlap with other neurological diseases. The purpose of the present study was to characterize the gait pattern in NPH quantitatively. Additionally, we analyzed the improvement of gait parameters following tapping of cerebrospinal fluid (CSF). METHODS: Gait analysis was performed in 10 patients and 12 age-matched healthy controls during overground and treadmill locomotion. RESULTS: Compared to healthy controls, patients with NPH walked significantly slower, with shorter and more variable strides and a somewhat lower cadence. The feet were not lifted to a normal height and the dorsal extension of the forefoot prior to heel-strike was insufficient. Balance-related gait parameters such as step width and the foot rotation angles were significantly increased in NPH, while their variability was lower. Only some gait parameters improved after tapping 30 ml CSF. Gait velocity increased by about 23% due to an increased stride length, while the cadence remained unchanged. Balance-related gait parameters and the foot-to-floor clearance during swing were not affected by the treatment. CONCLUSIONS: In conclusion, we found a triad of decreased stride length, decreased foot-to-floor clearance and a broad-based gait to be the typical features of the gait abnormality in NPH. Only the stride length improved following a diagnostic spinal tap. These results may help to more reliably diagnose the condition of NPH in a routine clinical setting.     

The predictive value of ventricular CSF removal in normal pressure hydrocephalus

We report the impact of diagnostic ventricular CSF removal (VCR) on the gait disturbance in 24 patients with suspected normal pressure hydrocephalus (NPH) who had an intraventricular catheter for studies of CSF dynamics in order to select patients for shunt surgery. There were no complications related to removal of 24 ml CSF over a period of 6 hours in four instances or to the removal of 15-18 ml at one time in twenty instances. Seventeen out of 24 patients were diagnosed as having NPH. Two of those patients who had relatively mild symptoms had a prolonged amelioration of their gait disturbance after diagnostic VCR. Thirteen patients underwent subsequent shunt operations. Eleven of them had good functional and symptomatic improvement on follow-up. In those six patients who had a marked amelioration of their gait disturbance after diagnostic VCR, not only improvement of the gait disturbance was observed after shunting, but a consistent overall improvement as well. The predictive value of VCR was more variable in those six patients who had only a moderate response to VCR. No change of the gait disturbance after VCR was noted in seven patients in whom the diagnosis of NPH was not confirmed. Diagnostic VCR might be a valuable ancillary test in specialized centers which routinely use intraventricular CSF monitoring in the selection of patients for shunt surgery. [Neural Res 1997; 19: 357-360]     

Hydrocephalus as a cause of disturbances of gait in the elderly

To investigate the possible role of symptomatic normal-pressure hydrocephalus (NPH) in unexplained walking difficulties of the elderly, we used CT to measure lateral ventricular size. We compared data in 50 patients over the age of 60 with a disturbance of gait and 80 control subjects of similar age who walked well and were mentally sound. Forty-six of the 50 gait patients (92%) had a ventricular span of more than 12 mm, whereas only 5 of the 80 controls (6.3%) had ventricles of that size. There was a narrow zone of overlap. Seventeen of the gait patients later improved after surgical shunting or test withdrawal of lumbar CSF. These findings demonstrate that hydrocephalus is an important cause of disturbances of walking in the elderly. The validity of the study, the clinical picture in NPH, and the nature of NPH are discussed.     

Gait disturbance in normal pressure hydrocephalus: a clinical study

The origin of gait disturbance in normal pressure hydrocephalus (NPH) is poorly understood. We assessed the frequency of frontal and sub-cortical hypokinetic gait clinical features and changes in gait variables after lumbar puncture (LP), in 15 patients with idiopathic NPH. Hypokinesia and disequilibrium were the main features, suggesting dysfunction of the basal ganglia (BG) and the frontal lobe (FL), respectively. Disequilibrium responded worse to LP and frontal signs were more frequent in patients that did not improve after LP. This could be related to earlier disturbance of frontal gait control.     

Gait disturbance in patients with low pressure hydrocephalus.

Using criteria of the classification recently described by Nutt et al., we examined gait disorder in five patients with normal pressure hydrocephalus (NPH). Their cerebrospinal fluid (CSF) pressures were in the normal range, and trials of CSF removal produced temporary improvement of symptoms. Surgical procedures to relieve hydrocephalus improved gait disorders in all patients. No patient showed spasticity, sensory ataxia, cerebellar ataxia, extrapyramidal signs, or limb apraxia. All walked slowly with a wide base and a short stride. The arm swing normally associated with walking was preserved. In standing, patients were unsteady and fell easily when pushed. Four patients showed hesitation in initiating walking and in turning. These clinical features fit Nutt's criteria for frontal gait disorder and frontal disequilibrium. Unlike findings in Parkinson's disease, where similar gait disorders may occur, other extrapyramidal signs, Myerson's sign, and upper limb dysfunction were absent in NPH, and arm swing while walking was preserved. We suspect that ventricular dilatation disturbs neuronal connections between the supplementary motor area and the globus pallidus in NPH patients.     

Normal-pressure hydrocephalus. Onset of gait abnormality before dementia predicts good surgical outcome

In 1977, Fisher reported that in patients with possible normal-pressure hydrocephalus (NPH), if the gait abnormality preceded dementia, surgery usually had a favorable outcome and vice versa. We studied this finding in 21 patients shunted for possible NPH. By evaluating serial videotapes of gait, neuropsychological tests, and Katz index ratings, preoperatively and at approximately two months and six months postoperatively, we judged 16 patients improved. In the improved group, the families reported that the gait abnormality preceded the dementia in 11 patients and occurred at the same time in five. In the unimproved group, dementia was noted first in three patients, gait abnormality first in one patient, and gait abnormality and dementia at the same time in one patient. Using Fisher's exact test, we compared the improved and unimproved groups for gait abnormality or dementia onset first and found a significant difference. We conclude that the history of gait abnormality occurring before or after dementia in patients with possible NPH is an important prognostic factor for surgical outcome.     

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.     

Normal-pressure hydrocephalus: white matter lesions correlate negatively with gait improvement after lumbar puncture

ObjectivesTo test relations between white matter lesions (WML) load in Normal Pressure Hydrocephalus (NPH) patients and gait characteristics at baseline, duration of symptoms, gait improvement after lumbar puncture (LP), vascular risk factors.PatientsFifteen idiopathic NPH patients.MethodsPatients underwent a timed walking test, before and after LP. Five gait variables were assessed and improvement percentages were calculated. WML load was rated regionally and globally in T2 weighted MRI images, using a simple visual scale. Spearman or Pearson correlation coefficients were used to test relations between variables.ResultsSignificant negative correlations were found between WML scores and gait improvement after CSF removal but not with duration of symptoms or gait variables before LP.ConclusionsWML seem to contribute to the irreversibility of symptoms in NPH but not to the pathophysiological mechanisms that lead to them.     

Psychotic symptoms in normal-pressure hydrocephalus.

Two patients with a psychiatric history of about 20 years, and clinical and neuroradiological signs of normal-pressure hydrocephalus (NPH) are reported. One had a periodic psychosis subsequent to a tuberculous meningitis, and this overshadowed the slight classical symptoms of NPH. She had received at least 120 treatments with electro-convulsive therapy. The second patient suffered from a paranoid psychosis; other signs of NPH were moderate though progressive. Both patients showed definite improvement of their NPH symptoms after ventriculo-atrial shunting, and psychotic symptoms ceased totally. Follow-up was 5 years for the patient with periodic psychosis. The other patient died from septicaemia 2.5 years after shunting. A large-scale screening of patients with psychiatric symptoms or dementia, particularly when combined with gait disturbance, should be done by using computerized tomography. Patients suspected of having NPH should then be referred for further examination with the aim of selecting patients suitable for shunting. These measures seem well motivated from humanitarian as well as economic points of view.     

Idiopathic normal pressure hydrocephalus: the CSF tap-test may predict the clinical response to shunting

A follow-up study was performed in nine patients with idiopathic normal pressure hydrocephalus (NPH) 37 months (mean) after shunting and 10 non-operated controls with comparable degrees of ventricular enlargement, gait disorder, and dementia. Five operated patients vs. no controls reported sustained general improvement (p<0.02). Objectively improved gait at follow-up (compared with preoperative status) was found in five of the six tested NPH-patients vs. none of the controls (p< 0.005). Improved gait and/or psychometric function was found in four of six NPH vs. none of eight control patients (p<0.02) after drainage of 40 ml cerebrospinal fluid (CSF tap-test). Improved gait during the CSF tap-test predicted continued improvement at follow-up. Temporal horn size was the only radiological variable which showed a (moderate) positive correlation with resistance to CSF absorption and rate of pressure increase. The size of the third ventricle diminished in parallell with clinical improvement.     

Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation

Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 ± 8.0 years-old), 17 AD patients (10 men, 72.1 ± 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 ± 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33 % relative to HC characterized AD (P < 0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3 % accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.     

Gait disturbances in Computer Dyno Graphy examination in patients with normal pressure hydrocephalus before and after surgery

BACKGROUND AND PURPOSE: Gait disturbances resulting from the normal pressure hydrocephalus (NPH) syndrome significantly restrain locomotion, which in serious cases can lead to a total loss of the ability to move. Hence the need to create an objective method of evaluating gait disturbances described by values of gait parameters and changes of these parameters resulting from neurosurgical treatment. The aim of this project is to create an effective, non-invasive diagnostics method describing movement disorders in patients with NPH before and after surgery. MATERIAL AND METHODS: An evaluation of the effectiveness of gait analysis was carried out with Ultraflex, which uses the Computer Dyno Graphy (CDG) system to measure the distribution of forces of reaction on the ground during walking. The control group consisted of 17 healthy individuals (age range 50-65 years) and the treatment group included 17 patients with enlargement of the ventricular system (9 females and 8 males, mean age 58.6 years, range 50-65 years), 8 of whom were qualified for surgical treatment. Analyzed parameters: ground reaction force, single and double support, stance. RESULTS: Changes of parameters reflected gait improvement. CONCLUSIONS: The results obtained indicate that gait analysis using the CDG system might be a good method for assessing the effectiveness of NPH surgery.     

Tau protein is a potential biological marker for normal pressure hydrocephalus

A biological marker for normal pressure hydrocephalus (NPH) is beneficial for evaluation of its severity and of indications for shunt operation. Tau protein was initially considered as a biological marker in cerebrospinal fluid (CSF) from Alzheimer's patients. Recently, it has been demonstrated that degeneration in the brain causes elevation of tau in CSF. Therefore, the tau level in CSF from NPH patients was evaluated. Tau levels in CSF from NPH patients were significantly higher than that in controls. The tau levels were correlated with the severity of dementia, urinary incontinence, and gait disturbance in NPH. These results suggest that CSF tau may be useful as a biological marker for NPH to determine the level of neuronal degeneration.     

Role of DESH,callosal angle and cingulate sulcus sign in prediction of gait responsiveness after shunting in iNPH patients

Primary endpoint of this single-centre, prospective consecutive cohort study was to evaluate DESH score, CA, CSS and Evans index of suspected iNPH patients against the reference standard of lumbar infusion test (LIT) and external lumbar drainage (ELD) in prediction of gait response after VP shunt implantation in patients with idiopathic normal pressure hydrocephalus (iNPH). Patients were assigned to NPH and non-NPH groups based on LIT and ELD results. Age-matched controls were added for group comparison. 32 NPH, 46 non-NPH and 15 control subjects were enrolled in the study. There were significant differences in mean preoperative DESH scores of NPH, non-NPH and control groups (6.3 ± 2.3 ([±SD]) (range 2–10) vs 4.5 ± 2.4 (range 0–10) vs 1.0 ± 1.2 (range 0–4)). Differences in mean CA and Evans index were not significant between NPH and non-NPH groups. CSS showed 62.5% sensitivity, 60.87% specificity, 52.63% PPV and 70% NPV for differentiation of NPH and non-NPH groups. A CA of 68 degrees had 48.49% sensitivity, 76.09% specificity, 59.26% PPV 67.31% NPV and DESH score of 4 had 93.75% sensitivity, 41.30% specificity, 52.63% PPV and 90.48% NPV for differentiation between NPH and non-NPH groups. The groups of probable iNPH patients with gait impairment diagnosed by high DESH score or positive functional testing did not overlap and DESH score did not correlate with gait improvement after ELD. DESH score should not be used as a simple diagnostic or prognostic marker of iNPH and we could not confirm the benefit of measurement of callosal angle and cingulate sulcus sign.     

Alzheimer's disease comorbidity in normal pressure hydrocephalus: prevalence and shunt response

The clinical impact of Alzheimer's disease pathology at biopsy was investigated in 56 cognitively impaired patients undergoing shunt surgery for idiopathic normal pressure hydrocephalus (NPH). Cognition was measured by means of the global deterioration scale (GDS), the mini mental status examination (MMSE) and a battery of six psychometric tests. Gait was assessed using objective measurements of velocity and the ambulatory index (AI). The prevalence of cases exhibiting neuritic plaques (positive biopsies) increased in parallel with dementia severity from 18% for patients with GDS 3 to 75% for patients with GDS scores > or =6. Patients with positive biopsies were more cognitively impaired (higher GDS and lower MMSE scores) as well as more gait impaired (higher AI scores and slower velocities) than patients with negative biopsies. After surgery, gait velocity and AI scores improved significantly and to a comparable degree for patients with and without positive biopsies. Similar proportions of positive and negative biopsy patients also had improved gait as assessed by means of subjective video tape comparisons. There were no significant differences between the biopsy groups in the magnitude of postoperative psychometric change or in the proportion of cases exhibiting improved urinary control. Alzheimer's disease pathology is a common source of comorbidity in older patients with idiopathic NPH where it contributes to the clinical impairment associated with this disorder. For patients accurately diagnosed with NPH, concomitant Alzheimer's disease pathology does not strongly influence the clinical response to shunt surgery.     

Normal pressure hydrocephalus in geriatric medicine: a challenge

Normal pressure hydrocephalus (NPH) in elderly patients is reviewed. Since the clinical signs that characterize NPH--incontinence, difficulty walking, and dementia--occur frequently in the elderly in association with a wide variety of disorders, attention is paid to the differential diagnosis of NPH on the basis of both clinical findings and laboratory tests. Success rates for treatment of NPH using surgical shunting are discussed, as are mortality rates and complication rates for this type of surgery in the elderly. Factors that may be of value in predicting which NPH patients are most likely to benefit from surgical intervention are reviewed, and the need for the development of pharmacological alternatives to surgery for elderly NPH patients is emphasized. As one of the most treatable causes of dementia in the elderly, NPH should be considered in the diagnosis of demented elderly patients with continence and gait disturbances, and it merits further research.     

Gait in drug naïve patients with de novo Parkinson's disease – altered but symmetric

Abstract

Background:

Motor symptoms in Parkinson's disease (PD) are typically asymmetrical. Early stage of PD is characterised with a predominantly unilateral appearance of tremor, rigidity and bradykinesia, with or without axial involvement. Also, studies have demonstrated gait asymmetry in de novo drug naïve PD patients. Aim of this study was to investigate gait pattern, gait symmetry and gait variability in early phases of PD.

Methods:

The gait was measured in 40 de novo, drug naïve PD patients and 43 healthy control subjects (HC) while performing a simple walking task. Calculated parameters were cycle time (CT), stride length (SL) and swing time (ST), and their coefficients of variation (CV).

Results:

Considering gait parameters, PD patients and HC differed in terms of all parameters, except for the CV of CT. Analysis of gait symmetry, comparison between the gait patterns of the left and the right leg in PD patients revealed no difference for any of the assessed parameters. The majority of the gait parameters did not differ between left and right legs of HC.

Conclusions:

It can be concluded that even gait was already altered in de novo drug naive PD patients, gait symmetry remained preserved. The SL was the most prominent parameter of altered gait in initial stages of PD patients, while the ST heralded postural asymmetry.     

Cognitive impairment in normal pressure hydrocephalus (NPH). A proposal for clinical evaluation protocol

Normal pressure hydrocephalus (NPH) is characterized by gait disturbance, urinary incontinence and dementia, and is associated with variable ventricular enlargement. The most accepted treatment of NPH is the placement of a cerebrospinal fluid shunt. Owing to the characteristics of the patients and the invasive nature of the surgical treatment, it is fundamental to detect those patients who could obtain a greater benefit from the treatment. Neuropsychological assessment of these patients could significantly contribute to a better diagnosis of NPH, determining a cognitive deterioration profile for these patients, allowing the assessment of treatment efficacy and helping to detect other additional causes of dementia. The aim of this study is to describe the cognitive deterioration profile of NPH patients and to present the clinical, functional and neuropsychological assessment protocol used in our hospital.