NOUS Andrew Tarnaris Neurosurgery

Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus

2011-10-14T19:07:00.000+01:00

Alzheimers Dement. 2011 Sep;7(5):501-8. doi: 10.1016/j.jalz.2011.01.003. Epub 2011 Jul 14.

Tarnaris A, Toma AK, Pullen E, Chapman MD, Petzold A, Cipolotti L, Kitchen ND, Keir G, Lemieux L, Watkins LD.

Source

Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, United Kingdom. andrewtarnaris@gmail.com

Abstract

INTRODUCTION:

It has still not been clearly established whether the cognitive deficits of idiopathic normal pressure hydrocephalus (iNPH) are caused by a disturbance in cerebrospinal fluid (CSF) dynamics or an underlying metabolic disturbance.

OBJECTIVE:

To identify the possible associations between biochemical markers, the neuroimaging characteristics, and cognitive deficits of patients undergoing investigations for possible iNPH.

METHODS:

A CSF sample obtained during a lumbar puncture from 10 patients with iNPH was analyzed for several biochemical markers (lactate, 8-isoprostane, vascular endothelial growth factor [VEGF], neurofilament heavy protein, glial fibrillary acidic protein, amyloid beta 1-42, and total tau). All patients underwent a battery of neuropsychological testing and imaging as part of their selection process for their suitability for CSF diversion surgical procedure. Volumetric analysis of imaging was carried out measuring the ventricular volume (VV), intracranial volume (ICV), periventricular lucencies, deep white matter hyperintensities, and white matter (WM) volume, as well as their ratios.

RESULTS:

A significant negative correlation of preoperative symptom duration and total tau levels (R = -0.841, P = .002) was found. There was a significant positive correlation (R = 0.648, P = .043) between the levels of VEGF and the VV/ICV ratio. There was a significant positive correlation of the levels of glial fibrillary acidic protein and the VV/deep white matter hyperintensities ratio (R = 0.828, P = .006). A significant negative correlation was observed between the levels of neurofilament heavy protein and the VV/ICV ratio (R = -0.657, P = .039) and the WM volume (R = -0.778, P = .023). Lactate levels were lower for patients performing in the normal range on the Recognition Memory Test for faces. Patients who performed better in the Recognition Memory Test words test had higher ICV volumes. All the patients in this study showed below normal performance when the subcortical function was assessed.

CONCLUSION:

The positive correlation of VEGF with the severity of ventriculomegaly may indicate that this is because of the transmantle pressure gradient; this response may not be because of hypoxia but represents an attempt at neuroregeneration. The degree of reactive gliosis correlates inversely with the severity of WM lesions. Neuronal degeneration is negatively correlated with the volume of the WM in these patients. The small association of volumetry and the cognitive profile of these patients may be consistent with a direct biochemical disturbance being responsible for the cognitive deficit observed. Ongoing studies with set protocols for neuropsychological assessment and volumetric analysis are warranted to further elucidate on the preliminary results of the current study

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2011-06-09T22:29:00.003+01:00

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2011-03-28T20:36:00.000+01:00

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Use of cerebrospinal fluid amyloid-β and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocep

2011-03-28T20:32:00.004+01:00

http://thejns.org/doi/abs/10.3171/2011.2.JNS101316 Andrew Tarnaris, M.R.C.S.1, Ahmed. K. Toma, F.R.C.S.(NS)1, Miles D. Chapman, Ph.D.2, Geoff Keir, Ph.D.2, Neil D. Kitchen, M.D., F.R.C.S.(SN)1, and Laurence D. Watkins, M.A., F.R.C.S.(SN)1 1Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery; and 2Department of Neuroimmunology, Institute of Neurology, Queen Square, London, United Kingdom Abbreviations used in this paper: Aβ1–42 = amyloid-β 1–42; AD = Alzheimer dementia; ELISA = enzyme-linked immunosorbent assay; iNPH = idiopathic normal pressure hydrocephalus. Address correspondence to: Andrew Tarnaris, M.R.C.S., Department of Neurosurgery, National Hospital for Neurology & Neurosurgery, Box 32, Queen Square, London WC1N 3BG. email: andrewtarnaris@gmail.com. Please include this information when citing this paper: published online March 25, 2011; DOI: 10.3171/2011.2.JNS101316. DOI: 10.3171/2011.2.JNS101316 Object The prognostic value of CSF biomarkers in patients with idiopathic normal pressure hydrocephalus (iNPH) has not been adequately studied to date. The aim of this study was to identify CSF markers of favorable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt. Methods Ventricular CSF was collected intraoperatively from 22 patients with iNPH and enzyme-linked immunosorbent assay was used to analyze the levels of amyloid-β 1–42 (Aβ1–42) and total tau protein. The Black grading scale was used to assess outcomes at 6 months. Receiver operating characteristic (ROC) curves were obtained and discriminant function analysis was undertaken to provide sensitivity and specificity figures for each marker as well as their combination. Results The mean age of the patients was 71.45 years (± 9.5 years [SD]). Follow-up was achieved in 21 patients. Seventeen patients had a favorable outcome and 4 patients had unfavorable outcome at 6 months. An Aβ1–42 level of 180 pg/ml had a sensitivity of 35% and a specificity of 20% for predicting a favorable outcome at 6 months. A total tau level of 767 pg/ml will have a sensitivity of 17% and a specificity of 20% for predicting a favorable outcome at 6 months. A combination of Aβ1–42 and total tau levels predicted favorable outcomes with a sensitivity of 80% and specificity of 82.4%. Conclusions In this pilot study a combination of Aβ1–42 levels and total tau protein levels predicted favorable surgical outcomes at 6 months with adequate accuracy to be of clinical use. Further study in a larger group with longer follow-up is warranted. KEYWORDS:hydrocephalus; normal pressure hydrocephalus; biomarkers; outcome; tau protein; amyloid-β.

Is there a difference in outcomes of patients with idiopathic intracranial hypertension with the choice of cerebrospinal fluid diversion site

2011-03-18T22:49:00.002Z

Clin Neurol Neurosurg. 2011 Mar 14. [Epub ahead of print]
Is there a difference in outcomes of patients with idiopathic intracranial hypertension with the choice of cerebrospinal fluid diversion site: A single centre experience.
Tarnaris A, Toma AK, Watkins LD, Kitchen ND.
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London WC 1N 3BG, UK.
Abstract
The visual and headache outcomes in patients with idiopathic intracranial hypertension (IIH) undergoing cerebrospinal fluid diversion with a lumboperitoneal (LPS) or ventriculoperitoneal shunting (VPS) have not been well reported. The aims of this study were to: (a) to assess outcomes of CSF diversion in IIH, (b) to understand influence of the type of shunt in outcomes, and (c) to understand factors predisposing in shunt failure.
METHODS: The medical records of 34 patients who underwent cerebrospinal fluid diversion (CSFD) between 1996 and 2007 were retrieved and epidemiological and clinical data was collected.
RESULTS: The mean age was 35 (±7.9) years. Thirty-four patients underwent 63 shunt placements in total. 85% follow-up was achieved. The mean follow-up for the entire group was 28.9 (±31.8) months. Headaches improved more than visual disturbances. There was no significant difference between the groups that received a VPS and those receiving an LPS in both headache and visual outcomes. The rate of complications was 20.5% and the need for revision was 35% for the whole group. Patients with LPS suffered more complications and first time revisions than patients with VPS. No factor recorded could predict the need for revision or final outcomes. The shunts of patients receiving a VPS tend to survive longer than those receiving primarily an LPS, however the difference is not statistically significant.
CONCLUSIONS: Predicting which patients will improve is not possible at present. The influence of site diversion is not critical but patients with VPS have less complications and revisions than those receiving a LPS.

Idiopathic Normal Pressure Hydrocephalus: Update and Practical Approach on Diagnosis and Management

2011-03-06T15:17:00.002Z

Andrew Tarnaris, MRCS,* and Michael A. Williams, MD, FAANw

The syndrome of idiopathic normal pressure hydrocephalus was first described in 1965, but 45 years later controversies still exist with regard to its cause, progression, differential diagnosis, and best treatment strategies. Its incidence may be underestimated and its importance increasing because of the aging population. The authors review current literature and offer an update on contemporary knowledge as well as a practical approach to diagnosis and management of the condition for the neurologists and neurosurgeons who encounter such patients.

(Neurosurg Q 2011;21:72–81)

http://journals.lww.com/neurosurgery-quarterly/Abstract/2011/02000/Idiopathic_Normal_Pressure_Hydrocephalus___Update.16.aspx

Rostrocaudal Dynamics of CSF Biomarkers.

2011-01-01T03:56:00.000Z

http://www.springerlink.com/content/b3834t464607028x/
Neurochem Res. 2010 Dec 30. [Epub ahead of print]
Rostrocaudal Dynamics of CSF Biomarkers.
Tarnaris A, Toma AK, Chapman MD, Petzold A, Keir G, Kitchen ND, Watkins LD.
The Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Box 32, Queen Square, London, WC, 1N 3BG, UK, andrewtarnaris@gmail.com.
Abstract
The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values.

Adjustable shunt valve-induced magnetic resonance imaging artifact: a comparative study.

2010-10-22T23:28:00.001+01:00

J Neurosurg. 2010 Jul;113(1):74-8.
http://thejns.org/doi/abs/10.3171/2010.8.JNS1067?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
Toma AK, Tarnaris A, Grieve JP, Watkins LD, Kitchen ND.
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom. ahmedktoma@yahoo.com
Abstract
OBJECT: In this paper, the authors' goal was to compare the artifact induced by implanted (in vivo) adjustable shunt valves in spin echo, diffusion weighted (DW), and gradient echo MR imaging pulse sequences.
METHODS: The MR images obtained in 8 patients with proGAV and 6 patients with Strata II adjustable shunt valves were assessed for artifact areas in different planes as well as the total volume for different pulse sequences.
RESULTS: Artifacts induced by the Strata II valve were significantly larger than those induced by proGAV valve in spin echo MR imaging pulse sequence (29,761 vs 2450 mm(3) on T2-weighted fast spin echo, p = 0.003) and DW images (100,138 vs 38,955 mm(3), p = 0.025). Artifacts were more marked on DW MR images than on spin echo pulse sequence for both valve types.
CONCLUSIONS: Adjustable valve-induced artifacts can conceal brain pathology on MR images. This should influence the choice of valve implantation site and the type of valve used. The effect of artifacts on DW images should be highlighted pending the development of less MR imaging artifact-inducing adjustable shunt valves.

Investigating shunt function using continuous intracranial pressure monitoring in adults: single center experience.

2010-10-22T23:26:00.002+01:00

J Neurosurg. 2010 Aug 27. [Epub ahead of print]
http://thejns.org/doi/abs/10.3171/2010.8.JNS1067?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
Toma AK, Tarnaris A, Kitchen ND, Watkins LD.
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.

Abstract
Object Managing symptomatic ventriculoperitoneal shunts with no clear evidence of shunt malfunction either clinically or radiologically can be a difficult task. The aim of this study was to assess intracranial pressure (ICP) monitoring as a method of investigating shunt function. Methods The authors performed a retrospective analysis of 38 continuous ICP monitoring procedures done in patients with ventriculoperitoneal shunts and suspected shunt malfunction. Results Thirty-eight procedures were performed in 31 patients between January 2005 and October 2008. Sixteen recordings were normal, 6 revealed overdrainage or low pressure, 11 indicated underdrainage or high pressure, and 5 showed variable shunt function. Based on the findings after 20 procedures (53%), patients were treated conservatively: 4 by readjusting the valve setting and 16 by referral to the headache neurologist for medical treatment. Forty-five percent of the conservatively treated patients improved. Surgical exploration was undertaken following 18 procedures (47%); 72% of the surgically treated patients improved. Conclusions Continuous ICP monitoring using an intraparenchymal probe is a safe and effective method of investigating adult hydrocephalus.

Working towards patient oriented outcome assessment in normal pressure hydrocephalus, what is the most important?

2010-10-22T23:25:00.000+01:00

Acta Neurochir (Wien). 2010 Aug 26. [Epub ahead of print]

Toma AK, Tarnaris A, Kitchen ND, Watkins LD.
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK, ahmedktoma@yahoo.com.
Abstract
OBJECTIVE: To date, there is no standard outcome assessment scale for shunt treatment in normal pressure hydrocephalus (NPH). In designing such scale, the relative weight of each of the common presentations of the condition from the patient's or his/her carer's point of view should be taken into consideration.
METHODS: A questionnaire was sent to 24 patients treated for NPH and their family/carer, assessing the patient and carer categorization of the preoperative main complaint, the weight they give to each of the common presentations of NPH and their satisfaction with treatment.
RESULTS: Twenty-two patients and 20 carers replied. Gait disturbance was the main complaint from both patient's (86%) and carer's (75%) point of view. Similarly, gait disturbance was considered as the most important problem that needs improvement by both patients (77%) and carers (65%). Incontinence was considered the second most important area by 11 (50%) patients and seven (35%) carers. When asked to quantify their satisfaction out of 10, patients had a mean of 7.2 while carers gave a mean of 7.5. Comparing subjective perspective of improvement with that of objective improvement on 10 m walking test and neuropsychological assessment, all patients who improved objectively were perceived as improved to a satisfactory degree by carers.
CONCLUSION: Walking/balance should be given far greater weight than other components of the NPH triad in future outcome assessment scales in accordance with patient/family perception.

Continuous intracranial pressure monitoring in pseudotumour cerebri: Single centre experience

2010-10-22T23:21:00.001+01:00

Br J Neurosurg. 2010 Oct;24(5):584-8.

Toma AK, Tarnaris A, Kitchen ND, Watkins LD.

Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. ahmedktoma@yahoo.com

OBJECTIVE: Investigating pseudotumour cerebri (PTC) patients who do not fulfil the diagnostic criteria, or those presenting post-shunt insertion with recurrent symptoms and signs, with no clear evidence of shunt malfunction, present a diagnostic challenge. PTC patients who underwent continuous intracranial pressure (ICP) monitoring in our unit were reviewed retrospectively.
RESULTS: Twenty-six ICP monitoring procedures were done on 20 patients. Eleven patients had normal pressure, 2 overdrainage/low pressure, 11 underdrainage/high pressure and 2 variable pressures. On the basis of these results 12 patients were managed conservatively: 11 patients were referred to headache team and 1 patient had readjustment of an adjustable valve shunt setting; of those 3 patients had improved symptoms on their first post-operative clinic review. On the other hand, 14 patients had surgery: 5 had shunt revision and 9 had shunt insertion; of those 5 patients improved.
CONCLUSION: ICP monitoring using an intraparenchymal probe is a safe and effective diagnostic technique in investigating PTC when indicated. A multidisciplinary approach achieves best results in terms of successful management and follow-up

Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus

2009-12-15T18:34:00.001Z

http://www.futuremedicine.com/doi/abs/10.2217/bmm.09.37

Idiopathic normal pressure hydrocephalus is a syndrome, which typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. Its diagnosis is based on relevant history and clinical examination, appropriate imaging findings and physiological testing. The clinical picture of idiopathic normal pressure hydrocephalus may occasionally be difficult to distinguish from that of Alzheimer’s dementia, subcortical ischemic vascular dementia and Parkinson’s disease. The aim of this article is to systematically review the literature from the last 29 years in order to identify cerebrospinal fluid (CSF) or imaging biomarkers that may aid in the diagnosis of the syndrome. The authors concluded that no CSF or imaging biomarker is currently fulfilling the criteria required to aid in the diagnosis of the condition. However, a few studies have revealed promising CSF and imaging markers that need to be verified by independent groups. The reasons that the progress in this field has been slow so far is also commented on, as well as steps required to apply the current evidence in the design of future studies within the field.

Normal pressure hydrocephalus: a reversible cause of dementia

2009-04-28T19:21:00.002+01:00

Laurence D Watkins, Andrew Tarnaris and Ahmed Toma

Send response to journal: Re: Normal pressure hydrocephalus: a reversible cause of dementia

We read with interest the review by Burns and Iliffe (BMJ 2009; 338:b75) with its very timely focus on dementia and its various causes। However, we were concerned that Normal Pressure Hydrocephalus (NPH) was mentioned only briefly। This condition perhaps deserves much greater emphasis, since it is a potentially reversible condition and may be a contributory factor in up to 5% of the dementia population.1 Normal pressure (or chronic adult) hydrocephalus affects the ageing population (usually over 60 years old) and typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. CSF pressure appears normal and brain imaging shows ventriculomegaly. Symptoms may be improved by surgical CSF diversion, especially if picked up early.2

Recent population-based studies have estimated the prevalence of NPH to be about 0।5% in those over 65 years old, with an incidence of about 5.5/100,000/year.3,4 Quality of life of patients treated by shunt insertion can improve substantially and the improvement can be long-lasting.5,6 Yet, less than 350 shunt insertion surgeries operations are performed in the UK for normal pressure hydrocephalus each year, representing a fraction of about 10% of the expected incidence (UK shunt registry, personal communication).

The authors mentioned that NPH should be excluded via neurocognitive assessment and (if available) computed tomogragraphy। Although CT scan of the brain is essential to establish ventriculomegaly as a prerequisite for the diagnosis of NPH,7 the sensitivity of neuropsychological assessment and brain imaging are low in diagnosing this condition and referral to specialized neurosurgical centre to conduct further testing by either lumbar drainage or assessment of CSF dynamics is essential.8

We certainly welcome the current expansion of services aimed at improving provision for dementia patients and would encourage inclusion of NPH in all diagnostic algorithms. It is important to consider the possible diagnosis if there is ventriculomegaly and the patient is fit enough to be a surgical candidate. If the diagnosis is being considered, then it should not be excluded except by invasive testing (such as extended lumbar drainage), which generally will mean referral to a specialist unit.9
References:
1. Silverberg G, Mayo M, Saul T, Fellmann J, McGuire D. Elevated cerebrospinal fluid pressure in patients with Alzheimers disease. Cerebrospinal Fluid Research 2006;3:7.
2. Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S4-16
3. Tanaka N, Yamaguchi S, Ishikawa H, Ishii H, Meguro K. Prevalence of Possible Idiopathic Normal-Pressure Hydrocephalus in Japan: The Osaki-Tajiri Project. Neuroepidemiology 2008;32(3):171-5.
4. Brean A, Eide PK. Prevalence of probable idiopathic normal pressure hydrocephalus in a Norwegian population. Acta Neurologica Scandinavica 2008;118(1):48-53.
5. Stein SC, Burnett MG, Sonnad SS. Shunts in normal-pressure hydrocephalus: do we place too many or too few? J Neurosurg 2006;105(6):815-22.
6. Pujari S, Kharkar S, Metellus P, Shuck J, Williams MA, Rigamonti D. Normal Pressure Hydrocephalus: Very long term outcome after shunt surgery. J Neurol Neurosurg Psychiatry 2008;79(11):1282-6
7. Tarnaris A, Kitchen ND, Watkins LD. Noninvasive biomarkers in normal pressure hydrocephalus: evidence for the role of neuroimaging. J Neurosurg. [Epub ahead of print] JNS, November 7, 2008; http://thejns.org/doi/abs/10.3171/2007.9.17572.
8. Marmarou A, Bergsneider M, Klinge P, Relkin N, Black PM. The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57(3 Suppl):S17-28.
9. Batra S, Rigamonti D. Idiopathic normal pressure hydrocephalus: the benefits and problems of shunting. Nat Clin Pract Neurol. 2009; 5(2):80-1.
Competing interests: The Clinical Research Fellow at Victor Horsley department of Neurosurgery at the National Hospital for Neurology and Neurosurgery salary is supported by a grant from B. Braun Medical Ltd

2009-02-18T00:15:00.000Z

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