Tag: Dementia

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Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes

Neurosurgery 94:1035–1043, 2024

Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs.

METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed.

RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09)

CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

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Cerebrospinal Fluid Shunting Improves Long-Term Quality of Life in Idiopathic Normal Pressure Hydrocephalus

Neurosurgery, Volume 86, Issue 4, April 2020: 574–582

The short- and long-term impact of cerebrospinal fluid shunting on quality of life (QoL) in idiopathic normal pressure hydrocephalus (INPH) is poorly understood.

OBJECTIVE: To investigate QoL in shunted INPH patients compared to the population and to investigate which factors influence QoL in INPH.

METHODS: INPH patients consecutively shunted in Sweden during 2008-2010 were scrutinized. Population-based controls were age- and sex-matched to the patients. Included participants were the following:176 INPH patients and 368controls.QoLwas assessed using the EuroQol 5-dimension 5-level (EQ5D5L) instrument, which measures overall QoL and health status in 5 dimensions. Independency (accommodation and/or need for in-home care) and comorbidities were assessed. Patients were followed up 6-45 mo after surgery (mean follow-up time: 21 mo).

RESULTS: Shunting improved QoL (P < .001) and health status in all dimensions (P < .005). Shunted INPH patients had lower QoL than controls (P < .001). The patients’health status in mobility, self-care, daily activities, and anxiety/depression was worse than the controls both before and after surgery (P < .001). The main predictors of low QoL in INPH were symptoms of depression (P < .001) and severity of gait disturbance (P = .001). Fewer INPH patients than controls lived independently (45% vs 85%, P < .001). Time after shunting had no influence on QoL.

CONCLUSION: QoL remains improved in shunted INPH patients at a mean follow-up time of 21 mo, but the patients do not reach the same QoL as the population. Symptoms of depression and severity of gait disturbance are the strongest predictors of low QoL in INPH.

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Comparison of the CSF dynamics between patients with idiopathic normal pressure hydrocephalus and healthy volunteers

J Neurosurg 131:1018–1023, 2019

Intracranial pressure (ICP), outflow resistance (R out ), and amplitude of cardiac-related ICP pulsations (AMPs) are established parameters to describe the CSF hydrodynamic system and are assumed, but not confirmed, to be disturbed in idiopathic normal pressure hydrocephalus (INPH). The aim of this study was to compare the CSF hydrodynamic profile between patients with INPH and healthy volunteers.

METHODS Sixty-two consecutive INPH patients (mean age 74 years) and 40 healthy volunteers (mean age 70 years) were included. Diagnosis was made by two independent neurologists who assessed patients’ history, neurological status, and MRI studies. A CSF dynamic investigation through the lumbar route was performed: ICP and other CSF dynamic variables were blinded to the neurologists during the diagnostic process and were not used for establishing the diagnosis of INPH.

RESULTS R out was significantly higher in INPH (R out 17.1 vs 11.1; p < 0.001), though a substantial number of INPH subjects had normal R out . There were no differences between INPH patients and controls regarding ICP (mean 11.5 mm Hg). At resting pressure, there was a trend that AMP in INPH was increased (2.4 vs 2.0 mm Hg; p = 0.109). The relationship between AMP and ICP was that they shared the same slope, but the curve was significantly shifted to the left for INPH (reduced P 0 [p < 0.05]; i.e., higher AMP for the same ICP).

CONCLUSIONS This study established that the CSF dynamic profile of INPH deviates from that of healthy volunteers and that INPH should thus be regarded as a disease in which intracranial hydrodynamics are part of the pathophysiology.

Clinical trial registration no.: NCT01188382 (clinicaltrials.gov)

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Deep brain stimulation for dementias

Neurosurg Focus 45 (2):E8, 2018

The aim of this article is to review the authors’ and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD).

METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events.

RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations.

CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.

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Bilateral deep brain stimulation of the fornix for Alzheimer’s disease

Bilateral deep brain stimulation of the fornix for Alzheimer’s disease

J Neurosurg 125:75–84, 2016

This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer’s disease (AD).

Methods The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure.

Results Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0–79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0–7.9 mm), y = 9.6 ± 0.9 mm (range 8.0–11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2–4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported.

Conclusions Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD.

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The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus

The callosal angle measured on MRI as a predictor of outcome in idiopathic normal-pressure hydrocephalus

J Neurosurg 120:178–184, 2014

Different neuroimaging biomarkers have been studied to find a tool for prediction of response to CSF shunting in idiopathic normal-pressure hydrocephalus (iNPH). The callosal angle (CA) has been described as useful in discriminating iNPH from ventricular dilation secondary to atrophy. However, the usefulness of the CA as a prognostic tool for the selection of shunt candidates among patients with iNPH is unclear. The aim of this study was to compare the CA in shunt responders with that in nonresponders and clarify whether the CA can serve as a predictor of the outcome.

Methods. Preoperative MRI brain scans were evaluated in 109 patients who had undergone shunt surgery for iNPH during 2006–2010. Multiplanar reconstruction was performed interactively to obtain a coronal image through the posterior commissure, perpendicular to the anterior-posterior commissure plane. The CA was measured as the angle between the lateral ventricles on the coronal image. The patients were examined clinically before surgery and at 12 months postoperatively.

Results. Shunt responders had a significantly smaller mean preoperative CA compared with nonresponders: 59° (95% CI 56°–63°) versus 68° (95% CI 61°–75°) (p < 0.05). A CA cutoff value of 63° showed the best prognostic accuracy.

Conclusions. The preoperative CA is smaller in patients whose condition improves after shunt surgery and may be a useful tool in the selection of shunt candidates among patients with iNPH.

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Biopsy of the Superficial Cortex: Predictors of Effectiveness and Outcomes

Biopsy of the Superficial Cortex

Neurosurgery 73:224–232, 2013 

Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking.

OBJECTIVE: We evaluated effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality.

METHODS: A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested.

RESULTS: Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.34-5.27, P < .01), previous cancer diagnosis (OR: 3.64, 95% CI: 1.69-7.85, P < .001), focal (OR: 3.90, 95% CI: 1.91-8.00, P< .001) and enhancing (OR: 5.03, 95% CI: 2.41-10.52, P< .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR: 9.34, 95% CI: 4.29-20.33, P < .001), and use of intraoperative navigation (OR: 6.59, 95% CI: 3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR: 2.51, 95% CI: 1.23-5.28, P < .05) and age older than 60 years (OR: 2.66, 95% CI: 1.36-5.18, P < .01).

CONCLUSION: Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.

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Poor Cognitive Outcome in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus

hydrocephalusNeurosurgery 72:1–8, 2013

Idiopathic normal pressure hydrocephalus (iNPH) causes cognitive decline that can be alleviated by shunting, but long-term outcome studies are scarce.

OBJECTIVE: To elucidate the long-term cognitive condition of shunt-responsive iNPH patients.

METHODS: The follow-up data (Kuopio University Hospital NPH Registry) of 146 patients diagnosed with iNPH by clinical and radiological examination, 24-hour intraventricular pressure monitoring, frontal cortical biopsy, and response to the shunt were analyzed for signs of dementia. The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, and specified memory disorder criteria were used. Median follow-up was 4.8 years.

RESULTS: At the end of follow-up, 117 (80%) of the 146 iNPH patients had cognitive decline and 67 (46%) had clinical dementia. The most common clinical diagnoses were Alzheimer disease and vascular dementia. In multivariate analysis of the 146 iNPH patients, memory deficit as a first symptom before shunt (odds ratio [OR] 18.3; 95% confidence interval [CI] 1.9–175), male sex (OR 3.29; 95% CI 1.11-9.73), age (OR 1.17 year; 95% CI 1.07-1.28), and follow-up time (OR 1.20 year; 95% CI 1.02-1.40) predicted dementia. Interestingly, 8 (5%) iNPH patients had dementia without any signs of other neurodegenerative diseases in clinical, neuroradiological, or brain biopsy evaluation. These patients initially presented a full triad of symptoms, with gait disturbance being the most frequent initial symptom followed by deterioration in cognition.

CONCLUSION: The novel findings were (a) a significant risk of dementia in iNPH initially responsive to cerebrospinal fluid shunt, (b) cognitive impairment most commonly due to iNPH-related dementia followed by concurrent degenerative brain disease, and (c) a subgroup with dementia related to iNPH without comorbidities.

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