[Treatment of Idiopathic Normal-Pressure Hydrocephalus by Wuling Powder Combined Ventriculo- peritoneal Shunt Surgery: an Efficacy Observation].

Objective To observe the clinical efficacy of Wuling Powder (WP) combined ventricu- loperitoneal shunt surgery in patients with idiopathic normal-pressure hydrocephalus (INPH). Methods Totally 56 INPH patients were randomly assigned to the control group and the treatment group, 28 in each group. All patients received ventriculoperitoneal shunt surgery. Three days after surgery patients in the treatment group took WP, while those in the control group took placebo decoction (one dose per day, once in the morning and once in the evening, 7 days as one course, a total of 6 courses after surgery). Mini- Mental State Examination (MMSE) score, the steps to turn around 180°, and Evan's index were tested be- fore surgery and 3 months after surgery. Adverse reactions were recorded in the two groups. Clinical effica- cy was assessed after 3 months of surgery. Results At month 3 after surgery 21 patients (80. 8%) were cured and 3 patients (11. 5%) were improved in the treatment group, with statistical difference when com- pared with the control group [14 cured (51. 9%) and 11 improved (40. 7%) ; P <0. 05]. Compared with be- fore surgery in the same group, levels of MMSE score increased and the steps to turn around 1800 were obviously reduced in the two groups at month 3 after surgery (both P <0. 05). Compared with the control group at month 3 after surgery, levels of MMSE score increased and the steps to turn around 1800 were ob- viously reduced in the treatment group (both P <0. 05). Conclusion In treating INPH patierts, WP com- bined ventriculoperitoneal shunt surgery was superior to the effect of using ventriculoperitoneal- shunt sur- gery alone.

Primary leptomeningeal B-cell lymphoma with normal pressure hydrocephalus at diagnosis.

An 80-year-old man, presenting with gait disturbance and memory loss, had findings of normal pressure hydrocephalus. Primary leptomeningeal lymphoma (PLML) was diagnosed based on cytology and flow cytometry of cerebrospinal fluid obtained by examination. Gadolinium-enhanced MRI showed enhancement of the brain and spinal cord but FDG-PET/CT revealed no lymph node swelling. With intrathecal chemotherapy, meningeal lesions disappeared and the gait disturbance and memory loss improved. However, the disease recurred three months later, manifesting as left facial nerve palsy, but the symptoms disappeared in response to intrathecal chemotherapy and systemic rituximab administration. Although a tumor lesion in the spinal canal was suggested by MRI examination, the patient has maintained a good clinical course for four years with intrathecal chemotherapy every three months. PLML is a very rare disease and its diagnosis is difficult. Repeated intrathecal chemotherapy appeared to be effective against PLML in this case.

Arterial Spin-Labeling Perfusion MR Imaging Demonstrates Regional CBF Decrease in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Regional cerebral blood flow has previously been studied in patients with idiopathic normal pressure hydrocephalus with imaging methods that require an intravenous contrast agent or expose the patient to ionizing radiation. The purpose of this study was to assess regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. A secondary aim was to compare the correlation between symptom severity and CBF. MATERIALS AND METHODS: Differences in regional cerebral perfusion between patients with idiopathic normal pressure hydrocephalus and healthy controls were investigated with pseudocontinuous arterial spin-labeling perfusion MR imaging. Twenty-one consecutive patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched randomly selected healthy controls from the population registry were prospectively included. The controls did not differ from patients with respect to selected vascular risk factors. Twelve different anatomic ROIs were manually drawn on coregistered FLAIR images. The Holm-Bonferroni correction was applied to statistical analyses. RESULTS: In patients with idiopathic normal pressure hydrocephalus, perfusion was reduced in the periventricular white matter (P < .001), lentiform nucleus (P < .001), and thalamus (P < .001) compared with controls. Cognitive function in patients correlated with CBF in the periventricular white matter (r = 0.60, P < .01), cerebellum (r = 0.63, P < .01), and pons (r = 0.71, P < .001). CONCLUSIONS: Using pseudocontinuous arterial spin-labeling, we could confirm findings of a reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic normal pressure hydrocephalus previously observed with other imaging techniques.

Adenosine Type A2A Receptor in Peripheral Cell from Patients with Alzheimer's Disease, Vascular Dementia, and Idiopathic Normal Pressure Hydrocephalus: A New/Old Potential Target.

As the European population gets older, the incidence of neurological disorders increases with significant impact on social costs. Despite differences in disease etiology, several brain disorders in the elderly (e.g., Alzheimer's disease, vascular dementia, normal pressure hydrocephalus) share dementia as a common clinical feature. The current treatment for the majority of these diseases is merely symptomatic and does not modify the course of the illness. Symptoms of normal pressure hydrocephalus are the only ones that can be modified if they are recognized in time and treated appropriately. Therefore, an important clinical strategy may be disclosed by pathogenic pathways that can be modified and to find drugs that can slow down or even arrest disease progression. Possibly a way to answer this question could be by re-examining all the molecules which have so far succeeded in improving many aspects of cognitive deterioration in some neurodegenerative conditions, that were not considered because of controversial opinions. The main purpose of this summary is to further substantiate the hypothesis that the pathway of adenosine type A2A receptor could be used as a potential target to develop new/old therapeutic strategies.

MRI assessment of the effects of acetazolamide and external lumbar drainage in idiopathic normal pressure hydrocephalus.

BACKGROUND: The objective was to identify changes in quantitative MRI measures in patients with idiopathic normal pressure hydrocephalus (iNPH) occurring in common after oral acetazolamide (ACZ) and external lumbar drainage (ELD) interventions. METHODS: A total of 25 iNPH patients from two clinical sites underwent serial MRIs and clinical assessments. Eight received ACZ (125-375 mg/day) over 3 months and 12 underwent ELD for up to 72 hours. Five clinically-stable iNPH patients who were scanned serially without interventions served as controls for the MRI component of the study. Subjects were divided into responders and non-responders to the intervention based on gait and cognition assessments made by clinicians blinded to MRI results. The MRI modalities analyzed included T1-weighted images, diffusion tensor Imaging (DTI) and arterial spin labelling (ASL) perfusion studies. Automated threshold techniques were used to define regions of T1 hypo-intensities. RESULTS: Decreased volume of T1-hypointensities and decreased mean diffusivity (MD) within remaining hypointensities was observed after ACZ and ELD but not in controls. Patients responding positively to these interventions had more extensive decreases in T1-hypointensites than non-responders: ACZ-responders (4,651 ± 2,909 mm(3)), ELD responders (2,338 ± 1,140 mm(3)), ELD non-responders (44 ± 1,188 mm(3)). Changes in DTI MD within T1-hypointensities were greater in ACZ-responders (7.9% ± 2%) and ELD-responders (8.2% ± 3.1%) compared to ELD non-responders (2.1% ± 3%). All the acetazolamide-responders showed increases in whole-brain-average cerebral blood flow (wbCBF) estimated by ASL (18.8% ± 8.7%). The only observed decrease in wbCBF (9.6%) occurred in an acetazolamide-non-responder. A possible association between cerebral atrophy and response was observed, with subjects having the least cortical atrophy (as indicated by a positive z-score on cortical thickness measurements) showing greater clinical improvement after ACZ and ELD. CONCLUSIONS: T1-hypointensity volume and DTI MD measures decreased in the brains of iNPH patients following oral ACZ and ELD. The magnitude of the decrease was greater in treatment responders than non-responders. Despite having different mechanisms of action, both ELD and ACZ may decrease interstitial brain water and increase cerebral blood flow in patients with iNPH. Quantitative MRI measurements appear useful for objectively monitoring response to acetazolamide, ELD and potentially other therapeutic interventions in patients with iNPH.

Lyme neuroborreliosis disguised as normal pressure hydrocephalus.

A 74-year-old woman presented with gait impairment, urinary incontinence, and dementia. She showed lymphocytic CSF pleocytosis and pronounced intrathecal Borrelia burgdorferi antibody production, indicating active Lyme neuroborreliosis. The syndrome of normal-pressure hydrocephalus (NPH) fully remitted after ceftriaxone treatment. Lyme neuroborreliosis may cause NPH by interfering with subarachnoid CSF flow.

Abnormal cisternogram associated with Diamox therapy.

A cisternogram characteristic of normal-pressure hydrocephalus was obtained from a patient on Diamox who was being evaluated for rapid mental deterioration. A repeat cisternogram after Diamox was discontinued was nearly normal. We hypothesize that the initial abnormality resulted from reduced cerebrospinal fluid production caused by carbonic anhydrase inhibition; this defect (reduced flow) led to a net reflux of tracer into the ventricles. The reflux is believed to be due to the reduction of bulk cerebrospinal fluid from the ventricles.

The pathophysiology of enlarged ventricles in normal pressure communicating hydrocephalus and schizophrenia: a possible therapeutic role for melatonin.

A dysfunction of the choroid plexus or the tela choroidae is suggested as the cause of ventricular enlargement in normal pressure communicating hydrocephalus and in some schizophrenic syndromes. In communicating hydrocephalus, the function of the tela choroidae could be impaired by infectious or inflammatory processes; while in schizophrenia a physiologic disorder of cerebrospinal fluid production due to a melatonin deficiency may result in dilated ventricles. Paradoxically, in both disorders, there is decreased production of cerebrospinal fluid.

Comment: the trouble with "n" in normal-pressure hydrocephalus.

Idiopathic normal-pressure hydrocephalus (iNPH) is a reversible syndrome of gait impairment, dementia, and incontinence that affects persons over 65 years of age.(1) Currently, the only effective treatment is surgical implantation of a shunt(2); however, the need for pharmacologic adjunctive treatments was noted at the 2005 NIH workshop on hydrocephalus.(3.)

Antisecretory factor (AF) exerts no effects on intracranial pressure (ICP) waves and ICP in patients with idiopathic normal pressure hydrocephalus and idiopathic intracranial hypertension.

BACKGROUND: Antisecretory factor (AF) and derivates thereof counteract brain edema and inflammation, and normalize ICP dynamics. The aim of the present study was to assess whether AF normalized the abnormal ICP waves, indicative of impaired intracranial compliance, seen in patients with idiopathic normal pressure hydrocephalus (iNPH) and idiopathic intracranial hypertension (IIH). The hypothesis was that brain swelling contributes to the abnormal ICP waves. METHODS: The study enrolled patients undergoing diagnostic ICP wave monitoring for either iNPH or IIH. The ICP waves and ICP were recorded continuously before and after oral administration of Salovum® (0.5 g/kg body weight/day divided by three doses), a freeze-dried egg yolk enriched in AF activity. Mean ICP wave amplitude (MWA), mean ICP wave rise time coefficient (MWRTC), and mean ICP were compared before and after Salovum® administration. RESULTS: A total of 10 iNPH patients and 8 IIH patients were included. No significant changes in the ICP wave indices or ICP were seen after Salovum® administration. Neither any significant time-dependent effect was observed. CONCLUSION: The lack of effect of Salovum® on ICP wave indices and ICP in iNPH and IIH may provide indirect evidence that brain swelling does not play a crucial role in the ICP wave indices or ICP of these conditions.

Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH.

OBJECTIVE: To assess the effects of low-dose acetazolamide treatment on volumetric MRI markers and clinical outcome in idiopathic normal-pressure hydrocephalus (iNPH). METHODS: We analyzed MRI and gait measures from 8 patients with iNPH with serial MRIs from an institutional review board-approved imaging protocol who had been treated off-label with low-dose acetazolamide (125-375 mg/day). MRI studies included fluid-attenuated inversion recovery and 3D T1-weighted high-resolution imaging. Automated analyses were employed to quantify each patient's ventricular, global white matter hyperintensities (WMH), and periventricular WMH (PVH) volumes prior to and throughout treatment. Clinical outcome was based on gait changes assessed quantitatively using the Boon scale. RESULTS: Five of 8 patients responded positively to treatment, with median gait improvement of 4 points on the Boon scale. A significant decrease in PVH volume (-6.1 ± 1.9 mL, p = 0.002) was seen in these patients following treatment. One patient's gait was unchanged and 2 patients demonstrated worsened gait and were referred for shunt surgery. No reduction in PVH volume was detected in the latter 2 patients. Nonperiventricular WMH and lateral ventricle volumes remained largely unchanged in all patients. CONCLUSIONS: These preliminary findings provide new evidence that low-dose acetazolamide can reduce PVH and may improve gait in iNPH. PVH volume, reflecting transependymal CSF, is shown to be a potential MRI indicator of pharmacologic intervention effectiveness. Further studies of pharmacologic treatment of iNPH are needed and may be enhanced by incorporating quantitative MRI outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that low-dose acetazolamide reverses PVH volume and, in some cases, improves gait in iNPH.

Preoperative acetazolamide SPECT is useful for predicting outcome of shunt operation in idiopathic normal pressure hydrocephalus patients.

PURPOSE OF THE REPORT: Good outcome of shunt surgery for idiopathic normal pressure hydrocephalus (iNPH) patients are highly dependent on accurate preoperative assessments. Acetazolamide ethylcysteinate-dimer-single photon emission computer tomography (SPECT) was applied to iNPH patients for more exact preoperative evaluation. PATIENTS AND METHODS: Sixty-five patients were categorized into 3 groups: group I (normals, n = 30), group II (with ventriculomegaly due to age-relating changes, n = 10), and group III (who underwent shunt surgery based on the diagnosis of iNPH, n = 25). Acetazolamide SPECT was performed in all patients, and mini-mental state examination (MMSE) was performed before and 1 month after the surgery in group III. RESULTS: Acetazolamide SPECT study demonstrated normal increase of cerebral blood flow (CBF, more than 40%) in groups I and II. Group III was classified into 2 subgroups on the examination; a mean increasing percentage (%increase) of CBF was less than 20% in group IIIa and more than 40% in group IIIb. One month after the surgery, acetazolamide SPECT showed normal %increase of CBF in IIIa, and the increase in postoperative MMSE score was significantly greater in group IIIa than IIIb (P < 0.05). In iNPH patients, less than 20% increase in preoperative acetazolamide SPECT predicted improvement of MMSE score with 100% sensitivity and 60% specificity. CONCLUSIONS: Poor %increase of CBF by acetazolamide implies a low capacity for vasodilation in the brain due to compression and stretching by ventriculomegaly. Acetazolamide SPECT study is not an absolute examination but one of the valuable supplementary objective examinations to determine the surgical indication in iNPH-suspected patients.

Syphilitic normal pressure hydrocephalus.

We report a case of presenile dementia with radiological and cisternographical features suggesting normal pressure hydrocephalus, caused by syphilitic infection. Treatment with penicillin resulted in considerable regression of the neurological and psychological signs.

Chronic Histoplasma capsulatum infection of the central nervous system successfully treated with fluconazole.

A 48-year-old man with a long-standing history of communicating hydrocephalus is reported. Ventriculoperitoneal shunting led to clinical improvement, but symptoms recurred despite surgical re-exploration switching the shunt to an atrial drainage. Ten months after the last surgical procedure, an acute myelopathy developed. Concomitant pharyngeal granuloma examination identified Histoplasma capsulatum (Hc) yeasts. Despite initial response to amphotericin B, Hc was isolated from cerebrospinal fluid (CSF), valve reservoir and distal catheter after two courses of therapy. Fluconazole successfully sterilized CSF, but transverse myelopathy persisted unchanged, and shunting was needed to control hydrocephalus.