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ARTICLE IN PRESS Clinical Neurology and Neurosurgery xxx (2013) xxx–xxx
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Successful treatment of negative pressure hydrocephalus using timely titrated external ventricular drainage: a case series夽 Benjamin H.M. Hunn a,b,∗ , Asim Mujic a , Idrees Sher a , Arvind K. Dubey a,b , Jens Peters-Willke a , Andrew W.M. Hunn a a b
Department of Neurosurgery, Royal Hobart Hospital, Hobart, Tasmania, Australia School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
a r t i c l e
i n f o
Article history: Received 4 October 2013 Accepted 27 October 2013 Available online xxx Keywords: Hydrocephalus Negative-pressure External ventricular drain
a b s t r a c t Objective: Negative-pressure hydrocephalus (NegPH) is a rare clinical entity characterised by enlarged ventricles and symptoms consistent with increased intracranial pressure (ICP) in the setting of negative ICP. Little has been published regarding appropriate treatment and outcomes of negative-pressure hydrocephalus patients, and no data have been published demonstrating successful therapy producing acceptable long-term outcomes. Here we present 8 cases successfully treated by titrated external ventricular drainage (TEVD), including drainage at negative (subatmospheric) pressure, and subsequent low-pressure ventriculoperitoneal shunting. Methods: A retrospective audit of all cases of negative-pressure hydrocephalus occurring at a university teaching hospital between 2006 and 2012 was undertaken. The clinical features of these cases, results of radiological investigations, treatment, and outcome were drawn from the patients’ records. Results: Eight cases of NegPH were identified. All patients had at least one preceding intracranial procedure (mean number of procedures 3.0). All cases were treated using TEVD, titrated to produce between 5 and 15 mL per hour of CSF drainage, including drainage under subatmospheric pressure if this was required to maintain CSF flow. Mean delay from first negative ICP to TEVD was 1.8 days. All 8 patients demonstrated clinical improvement. TEVD resulted in improvement in Glasgow Coma Scale (mean increase 4.6, p = 0.003), and increases in ICP (mean increase 8.5, p < 0.001). Mean length of follow-up was 471.8 days. At follow-up, four patients had returned to pre-morbid functioning, three had a reduction in functioning attributable to their initial presentation (not NegPH), and one had died of unknown cause. Illustrative case descriptions are included. Conclusions: Negative-pressure hydrocephalus is a rare but underrecognised syndrome that can be successfully treated by timely external ventricular drainage titrated to maintain CSF flow, and subsequent low-pressure ventriculoperitoneal shunting. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Negative-pressure hydrocephalus (NegPH) is a rare condition that is characterised by enlarged ventricles and symptoms consistent with increased intracranial pressure in the setting of negative intracranial pressure (ICP). The first description of NegPH was provided by Vassilyadi et al., who reported 2 paediatric patients with
夽 Portions of this work were presented in an electronic presentation at the 81st Annual Scientific Meeting of the American Association of Neurological Surgeons, New Orleans, United States, April 27, 2013. ∗ Corresponding author at: School of Medicine, University of Tasmania, Private Bag 68, Hobart, Tasmania 7000, Australia. Tel.: +61 3 6226 2660; fax: +61 3 6226 4824. E-mail address: [email protected] (B.H.M. Hunn).
hydrocephalic symptoms, negative ICP, and clinical improvement with modification of cystopleural shunts to increase flow resistance [1]. Since this initial report, a total of five further cases have been reported in the literature, by Clarke and her colleagues, and Fillipidis et al. [2,3]. In 2006, Clarke et al. described two cases of likely NegPH treated with negative-pressure drainage of cerebrospinal fluid (CSF) and clinical response that was initially promising. Unfortunately, ultimate clinical outcome in both cases was poor; both patients were non-verbal at follow-up, one was bedridden and the other had been admitted to a residential care facility [2]. Notable in this series was a prolonged time from initial symptoms to ultimate treatment with external ventricular drainage. In 2011, Fillipidis et al. described a further 3 patients with low or negative-pressure hydrocephalus following surgical approaches to the cranial base [3]. Two of these patients improved with repair of CSF leaks and external ventricular drainage that was titrated to produce CSF
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Please cite this article in press as: Hunn BHM, et al. Successful treatment of negative pressure hydrocephalus using timely titrated external ventricular drainage: a case series. Clin Neurol Neurosurg (2013), http://dx.doi.org/10.1016/j.clineuro.2013.10.019
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ARTICLE IN PRESS
Alive 63 8
Aneurysmal subarachnoid haemorrhage
70 7
M
F 54 6
F
M M 12 36 4 5
Aneurysmal subarachnoid haemorrhage Left MCA aneurysm, elective clipping
M F 51 65 2 3
Tectal plate cavernoma Metastatic adenocarcinoma of unknown origin Severe traumatic brain injury Severe traumatic brain injury
M 27 1
Pineal germinoma
Primary disease process Sex Age (y) Case number
Eight patients met the inclusion criteria, and relevant clinical details are summarised in Table 1. 5 were males. The teaching hospital from which these cases arose has a well-defined catchment population, which enabled estimation of the incidence of NegPH at 1 case per 380 250 people per year. The mean age at development of NegPH was 47.3 years (range 12–70 years, standard deviation (SD): 20.4 years). All patients had at least 1 preceding neurosurgical procedure, with the mean number of procedures 3.0 per patient (range 1–7, SD: 2.0). All patients were treated by external ventricular drainage that was titrated to maintain CSF flow volumes of between 5 and 15 mL per hour (titrated external ventricular drainage, TEVD), depending on clinical progress. This included negative-pressure drainage if this was required to maintain CSF flow. Negativepressure drainage was required in 6 cases. The mean time from first measured negative ICP to commencement of TEVD was 1.8 days (range 0–8 days, SD: 2.7 days). The mean duration of TEVD was 3.2 days (range 1–5 days, SD: 1.5 days). ICP prior to TEVD averaged −3.1 centimetres of water (cmH2 O) (range −1 to −7 cmH2 O, SD: 1.9 cmH2 O). Lowest recorded ICP averaged −6.5 cmH2 O (range −3 to −14 cmH2 O, SD: 1.9 cmH2 O). Average ICP following TEVD was 5.0 cmH2 O (range 2–7 cmH2 O, SD 1.9). The difference between ICP before and after TEVD was significantly different (mean increase 8.5 cmH2 O, p < 0.001). Mean GCS prior to TEVD was 9.4 (range 5–14, SD: 2.9). Following TEVD mean Glascow Coma Scale (GCS) was 14
Table 1 Characteristics of negative-pressure hydrocephalus patients.
3. Results
EVD, external ventricular drain; MCA, middle cerebral artery; VPS, ventriculoperitoneal shunt.
37 VPS with Medtronic Strata NSC valve set at 0.5
Dead 48 VPS with Medtronic Strata NSC valve set at 0.5
Alive 100 VPS with Medtronic Strata NSC valve set at 0.5
Alive Alive 345 200 VPS with Medtronic Strata II valve set at 1.0 VPS with Medtronic Strata NSC valve set at 0.5
Alive
Alive Alive 806 700 VPS with Medtronic Strata NSC valve set at 0.5 VPS with Medtronic Strata NSC valve set at 0.5
Definitive therapy
Length of follow-up (days)
Alive/dead
A retrospective audit of all neurosurgical cases occurring between 2006 and 2012 at a university teaching hospital was undertaken to identify cases of NegPH. Cases were drawn from the neurosurgical patient database. Cases were included if (i) a negative ICP was measured, (ii) there was concurrent radiographic evidence of ventriculomegaly, (iii) the patient was suffering symptoms that were attributable to hydrocephalus and coincided temporally with negative ICP and ventriculomegaly, and (iv) malfunction of the ICP monitor and other equipment had been excluded. ICP was monitored using strain gauge tipped intracranial catheters manufactured by Codman (Raynham, Massachusetts, USA), or via an external ventricular drain (EVD) (in all cases manufactured by Medtronic, Minneapolis, Minnesota, USA). EVDs were levelled to the tragus at the beginning of each nursing shift. Clinical parameters were monitored by trained neurosurgical nurses in a neurosurgical high dependency unit. Computed tomography (CT) scans were performed using a Siemens Somatom Definition AS scanner (Erlangen, Germany). Data was gathered on patients’ clinical parameters, including previous procedures, longitudinal data on ICPs, conscious state, treatment of NegPH, and outcome data. Statistical tests were performed using GraphPad Prism 6 (Graphpad Software, California, USA). Two-tailed paired t-tests were performed for continuous variables measured on each patient. A P value of less than 0.05 was used to determine significance.
1538
2. Materials and methods
VPS with Medtronic Strata II valve set at 0.5
Functional outcome
flow; both of these cases required drainage under subatmospheric pressures. Ultimately, one of these patients was provided with a ventriculoperitoneal shunt (VPS), and one was palliated due to poor progress. Their third case demonstrated clinical improvement solely with repair of a frontal CSF leak. In this paper we present the first series describing statistically significant clinical, manometric, and radiological improvement following treatment for NegPH, with data on long-term patient outcomes.
Returned to work and premorbid function CN VI palsy, balance difficulty Undergoing chemotherapy, balance difficulty Attending school with teaching aides Returned to premorbid function, mobilising with support Returned to work and premorbid function Discharged to an external hospital, died of unknown cause 48 days later Returned to work and premorbid function
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Please cite this article in press as: Hunn BHM, et al. Successful treatment of negative pressure hydrocephalus using timely titrated external ventricular drainage: a case series. Clin Neurol Neurosurg (2013), http://dx.doi.org/10.1016/j.clineuro.2013.10.019
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Fig. 1. Left: Change in ICP following TEVD. *p = 0.003, two-tailed paired t-test. Right: Change in GCS following TEVD. *p < 0.001, two-tailed paired t-test. GCS, Glasgow coma scale; ICP, intracranial pressure; TEVD, titrated external ventricular drainage.
(range 12–14, SD: 0.9). There was a statistically significant improvement in GCS following TEVD (mean increase 4.6, p = 0.003) (Fig. 1). Following cessation of TEVD, all patients underwent definitive treatment using low-pressure VPS. All shunts were fitted with programmable valves manufactured by Medtronic (Minneapolis, Minnesota, USA). No antisiphon devices were included in the shunt systems. 7 patients had valves programmed at setting 0.5 (approximately equivalent to 20 millimetres of water (mmH2 O)). Patient 4 had his valve set at 1.0 (approximately equivalent to 40 mmH2 O). The mean duration of follow-up was 471.8 days (range 37–1538, SD: 520.6). At follow-up 7 patients were alive. Patient 7 died 48 days following discharge to an external hospital, and no autopsy was performed to definitively ascertain cause of death. At followup 4 patients had regained their pre-morbid level of functioning. Of the remaining 3 surviving patients, all had sequelae that could be attributed to their primary disease process (Table 1).
4. Illustrative cases 4.1. Patient 3 A 65 year-old female was referred to our service with acute hydrocephalus of unknown aetiology and reduced conscious state (GCS 9) (Fig. 2A). There was no evidence on magnetic resonance studies of an obstructive lesion to account for the development of hydrocephalus. Lumbar puncture demonstrated increased CSF protein, but no other abnormalities. She underwent urgent insertion of an EVD; although pressures were initially elevated, after 2 h measured ICP ranged from 2 to −2 cmH2 O. Over the following 2 days there was minimal CSF drainage and no clinical improvement (Fig. 2B). On the third post-operative day the decision was made to titrate the height of drainage to maintain CSF flow volumes at 5 mL per hour, including drainage at subatmospheric pressures as required. This resulted in rapid improvement in conscious state, such that after drainage of 35 mL over seven hours the GCS was 14. Drainage continued under negative pressures for 5 days (Fig. 2C), following which a VPS was placed with a Medtronic Strata NSC Valve set at 0.5. Subsequent to her discharge it became apparent that her initial condition may have been due to cerebellar metastatic adenocarcinoma of unknown origin, and she underwent chemotherapy and subsequent surgical decompression of the cerebellum. At 23 months following titrated drainage and lowpressure VPS, there was no radiographic or clinical evidence of hydrocephalus recurrence (Fig. 2D).
4.2. Patient 8 A 63 year-old male suffered an aneurysmal subarachnoid haemorrhage (Hunt and Hess grade V) originating from an aneurysm of the anterior communicating artery, which was complicated by acute hydrocephalus (Fig. 2E). He was transferred to our with a GCS of 3, and underwent urgent insertion of an EVD, with drainage of 100 mL of blood-stained CSF over the following 12 h at a drainage height of 15 cm. On the following day he underwent craniotomy and clipping of the aneurysm. Post-operative digital subtraction angiography demonstrated a residual aneurysmal defect that was clipped on the third day following presentation. The patient continued to improve, such that on the twentieth day following presentation his GCS was 11, ICP had normalised, and the EVD was removed. In the 2 days following removal of the EVD the patient demonstrated a marked deterioration to a GCS of 8. CT of the brain showed marked dilatation of the ventricles, consistent with communicating hydrocephalus (Fig. 2F). Another EVD was subsequently inserted, and ICP measurements through this device were very low, between 0 and 5 cmH2 O. Negativepressure drainage was commenced over 24 h to maintain CSF drainage at 8 mL per hour. During this period GCS improved from 8 to 14 (Fig. 2G). 7 days after re-insertion of an EVD, a VPS was placed with a Medtronic programmable valve without an antisiphon device, with a valve setting of 0.5. He was subsequently discharged home, and one month following discharge had returned to work, and there was no further evidence of hydrocephalus (Fig. 2H).
5. Discussion 5.1. Pathogenesis of negative-pressure hydrocephalus Hydrocephalic states without elevated ICP first gained widespread recognition following the description by Adams and colleagues of what became known as normal-pressure hydrocephalus (NPH) [4]. NPH is characterised by pathological enlargement of the ventricles with normal opening pressures on lumbar puncture, and a triad of clinical symptoms that include dementia, gait ataxia, and urinary incontinence [4]. Adams et al. demonstrated resolution of dementia in a significant proportion of their study population following ventriculoperitoneal shunting of CSF [4]. Further studies demonstrated the utility of refined patient selection to better target ventriculoperitoneal shunting to those
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Fig. 2. (A–D) Patient 3, a 65 year-old female who presented with acute hydrocephalus. (E–H) Patient 8, a 63 year-old male who presented following an aneurysmal subarachnoid haemorrhage. (A and E) CT scan at initial presentation. (B and F) CT scans demonstrating ventriculomegaly associated with NegPH. (C and G) CT scans following TEVD. (D and H) CT scans at last follow-up (described in Table 1). NegPH, negative-pressure hydrocephalus; TEVD, titrated external ventricular drainage.
patients with true NPH, rather than conditions with similar symptoms such as vascular dementia or Alzheimer’s disease [5–7]. The pathogenic alterations underlying NPH and its symptomatology have been extensively researched since its original description. Key features thought to underlie the NPH disease process include ongoing “high-normal” CSF pressures, white matter changes, and alterations to cerebral blood flow [8–10]. Interestingly, it has recently been demonstrated that clinical improvement in NPH, at least with CSF drainage via lumbar puncture, does not correlate with change in ventricular size [11]. This may indicate that clinical improvement in NPH is due to reduction of total brain water and alterations in brain compliance and homeostasis, rather than change in ventricular size. More recently, the literature has described multiple cases of low-pressure hydrocephalus (LPH). LPH was first described by Pang & Altschuler in 1994, in 12 children who had initially undergone medium-pressure ventriculoperitoneal shunting for treatment of hydrocephalus [12]. All twelve children presented with a hydrocephalic syndrome, in the setting of low intracranial pressures. Resolution of symptoms occurred following drainage of CSF under subatmospheric pressures. Since Pang & Altschuler’s initial report, several other authors have described cases of low-pressure hydrocephalus [13–15]. Multiple mechanisms have been suggested for the pathogenesis of LPH. In their early work on the subject, Pang & Altschuler described their theory of alterations in the viscoelastic modulus of the brain, mediated by reduced brain extracellular fluid content secondary to prolonged overstretching of the brain parenchyma. In this hypothesis, distortion of brain tissue results in symptoms by way of cortical ischaemia and elevated compressive stresses within the brain [12]. Although this hypothesis has not been tested in LPH, reduction in cerebral blood flow is known to occur in NPH, and has been demonstrated to normalise following CSF drainage and resolution of ventriculomegaly [9,16]. In 2002, Lesniak et al. enlarged on the work of Pang & Altschuler, using the concept of elastic hysteresis to demonstrate that when brain compliance is altered, ventriculomegaly can persist at an intracranial pressure that would previously have resulted in normal ventricular volume [14]. Virtual simulations have also emphasised the role brain turgor has in the pathogenesis of inappropriately low-pressure hydrocephalus [17]. Treatment of LPH has been investigated by Hamilton
& Price, who found that endoscopic third ventriculostomy was beneficial in reducing the number of patients requiring a permanent VPS [18]. In some of the only work published regarding NegPH, Fillipidis and colleagues suggest that CSF leaks play a pivotal role in the development of a negative-pressure hydrocephalic state, by producing a very-low subarachnoid pressure [3]. Very-low subarachnoid pressures in turn produce a transmantle pressure gradient that generates a state in which ventriculomegaly can persist with negative ICP. The initial cause of ventriculomegaly may be a blockage between the ventricles and the subarachnoid space, possibly caused by haemorrhage into the CSF. These hypotheses are supported by the fact that every reported case of NegPH, including our series, features a prior surgical operation disrupting pressure homeostasis, and therefore also a potential source of haemorrhage, however minor. Furthermore, the fundamental importance of cortical subarachnoid space disruption in the development of lowpressure hydrocephalic states has been emphasised by computer modelling [19]. It is possible that several aetiologic mechanisms are at play in NegPH; CSF leaks and blood products within the CSF precipitate ventriculomegaly, and associated with this brain water and compliance are altered. This creates a state in which ventriculomegaly can persist with negative ICP. Changes in neuronal homeostasis and cerebral blood flow may manifest as the clinical presentation described in our patients. TEVD is therefore required in order to “reset” parenchymal compliance to its normal state, in accordance with the theory of elastic hysteresis provided by Lesniak et al. in regards to LPH [14]. NegPH likely lies on one extreme of a continuum of pressure–volume relationships within the cranial vault, with prototypical cases of acute hydrocephalus that adhere to the Monro-Kellie doctrine at the other extreme. NPH and LPH occupy the spectrum between these two extremes. More cases of NegPH are required before definitive statements regarding the pathogenesis of this disease can be made. Indeed, the true pathogenesis of NegPH is likely to remain obscure until the nature of physiological CSF production has been fully elucidated. Current evidence suggests that CSF production and metabolism is much more dynamic and geographically diverse than traditionally taught [20,21].
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5.2. Suggested clinical approach In all cases where a patient’s neurological state deteriorates, and there is clinical suspicion of hydrocephalus, imaging should be performed to confirm the diagnosis. Subsequent EVD insertion and pressure monitoring should proceed if this is clinically appropriate. In those cases where there are positive ICPs and CSF drainage is adequate, standard care should follow. In the very small minority of cases where negative ICPs exist or develop, there is impairment of CSF drainage, and persistent ventriculomegaly, the patient should be admitted to a neurosurgical high-dependency unit for intensive monitoring of neurological state and ICPs. The draining pressure of the EVD should be titrated to achieve 5–10 mL per hour of CSF drainage. If clinical and manometric improvement does not follow, it may be necessary to re-titrate to higher drainage targets. The focus should be on targeted drainage volume, rather than targeted ICP. The key concern in treating a patient with TEVD is that low or negative pressures may be required to produce CSF flow, and that this may cause subdural effusion. This risk needs to be balanced against the potential benefit of TEVD in each patient. Following clinical and manometric resolution of NegPH, some degree of ventriculomegaly may persist, associated with relatively low ICPs. Essentially, a low-pressure hydrocephalic state has now been created. In this series we have described successful treatment using low-pressure ventriculoperitoneal shunting as the final therapy in resolving NegPH. 6. Conclusion In this case series we present the first data demonstrating successful long-term treatment of patients suffering from NegPH. The critical points illustrated by our work are the importance of early recognition and prompt treatment of NegPH. Future research should aim to provide evidence to cement or disprove the proposed treatment regime, and also to describe etiologic factors for NegPH, such that it may be prevented. Acknowledgements The authors would like to thank their colleagues for support and critical appraisal of methods and manuscripts. References
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[2] Clarke MJ, Maher CO, Nothdurft G, Meyer F. Very low pressure hydrocephalus – report of two cases. J Neurosurg 2006;105:475–8. [3] Filippidis AS, Kalani YS, Nakaji P, Rekate HL. Negative-pressure and lowpressure hydrocephalus: the role of cerebrospinal fluid leaks resulting from surgical approaches to the cranial base report of 3 cases. J Neurosurg 2011;115:1031–7. [4] Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. Symptomatic occult hydrocephalus with normal cerebrospinal-fluid pressure. N Engl J Med 1965;273:117–26. [5] Marmarou A, Young HF, Aygok GA, Sawauchi S, Tsuji O, Yamamoto T, et al. Diagnosis and management of idiopathic normal-pressure hydrocephalus: a prospective study in 151 patients. J Neurosurg 2005;102: 987–97. [6] Black PML. Idiopathic normal-pressure hydrocephalus. J Neurosurg 1980;52:371–7. [7] Marmarou A, Bergsneider M, Klinge P, Relkin N, Black PML. The value of supplemental prognostic tests for the preoperative assessment of idiopathic normal-pressure hydrocephalus. Neurosurgery 2005;57:S2–17. [8] Graff-Radford NR, Rezai K, Godersky J, Eslinger P, Damasio H, Kirchner P. Regional cerebral blood flow in normal pressure hydrocephalus. J Neurol Neurosurg Psychiatr 1987;50:1589–96. [9] Momjian S, Owler BK, Czosnyka Z, Czosnyka M, Pena A, Pickard JD. Pattern of white matter regional cerebral blood flow and autoregulation in normal pressure hydrocephalus. Brain 2004;127:965–72. [10] Krauss JK, Regel JP, Vach W, Orszagh M, Jüngling FD, Bohus M, et al. White matter lesions in patients with idiopathic normal pressure hydrocephalus and in an age-matched control group: a comparative study. Neurosurgery 1997;40:491–6. [11] Lenfeldt N, Hansson W, Larsson A, Birgander R, Eklund A, Malm J. Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus. Neurology 2012;79:237–42. [12] Pang DL, Altschuler E. Low-pressure hydrocephalic state and viscoelastic alterations in the brain. Neurosurgery 1994;35:643–55. [13] Owler K, Jacobson E, Johnston I. Low pressure hydrocephalus: issues of diagnosis and treatment in five cases. Br J Neurosurg 2001;15:353–9. [14] Lesniak MS, Clatterbuck RE, Rigamonti D, Williams MA. Low pressure hydrocephalus and ventriculomegaly: hysteresis, non-linear dynamics, and the benefits of CSF diversion. Br J Neurosurg 2002;16:555–61. [15] Akins PT, Guppy KH, Axelrod YV, Chakrabarti I, Silverthorn J, Williams AR. The genesis of low pressure hydrocephalus. Neurocrit Care 2011;15: 461–8. [16] Tanaka A, Kimura M, Nakayama Y, Yoshinaga S, Tomonaga M. Cerebral blood flow and autoregulation in normal pressure hydrocephalus. Neurosurgery 1997;40:1161–5. [17] Rekate HL. Brain turgor (Kb): intrinsic property of the brain to resist distortion. Pediatr Neurosurg 1992;18:257–62. [18] Hamilton MG, Price AV. Inappropriately low-pressure (negative-pressure) hydrocephalus: experience with 20 patients examining the role for endoscopic third ventriculostomy. Neurosurgery 2010;67:553. [19] Rekate HL, Nadkarni TD, Wallace D. The importance of the cortical subarachnoid space in understanding hydrocephalus. J Neurosurg Pediatr 2008;2: 1–11. [20] Brodbelt A, Stoodley M. CSF pathways: a review. Br J Neurosurg 2007;21:510–20. [21] Bulat M, Klarica M. Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev 2011;65:99–112.
[1] Vassilyadi M, Farmer JP, Montes JL. Negative-pressure hydrocephalus. J Neurosurg 1995;83:486–90.
Please cite this article in press as: Hunn BHM, et al. Successful treatment of negative pressure hydrocephalus using timely titrated external ventricular drainage: a case series. Clin Neurol Neurosurg (2013), http://dx.doi.org/10.1016/j.clineuro.2013.10.019
ARTICLE IN PRESS Clinical Neurology and Neurosurgery xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Successful treatment of negative pressure hydrocephalus using timely titrated external ventricular drainage: a case series夽 Benjamin H.M. Hunn a,b,∗ , Asim Mujic a , Idrees Sher a , Arvind K. Dubey a,b , Jens Peters-Willke a , Andrew W.M. Hunn a a b
Department of Neurosurgery, Royal Hobart Hospital, Hobart, Tasmania, Australia School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
a r t i c l e
i n f o
Article history: Received 4 October 2013 Accepted 27 October 2013 Available online xxx Keywords: Hydrocephalus Negative-pressure External ventricular drain
a b s t r a c t Objective: Negative-pressure hydrocephalus (NegPH) is a rare clinical entity characterised by enlarged ventricles and symptoms consistent with increased intracranial pressure (ICP) in the setting of negative ICP. Little has been published regarding appropriate treatment and outcomes of negative-pressure hydrocephalus patients, and no data have been published demonstrating successful therapy producing acceptable long-term outcomes. Here we present 8 cases successfully treated by titrated external ventricular drainage (TEVD), including drainage at negative (subatmospheric) pressure, and subsequent low-pressure ventriculoperitoneal shunting. Methods: A retrospective audit of all cases of negative-pressure hydrocephalus occurring at a university teaching hospital between 2006 and 2012 was undertaken. The clinical features of these cases, results of radiological investigations, treatment, and outcome were drawn from the patients’ records. Results: Eight cases of NegPH were identified. All patients had at least one preceding intracranial procedure (mean number of procedures 3.0). All cases were treated using TEVD, titrated to produce between 5 and 15 mL per hour of CSF drainage, including drainage under subatmospheric pressure if this was required to maintain CSF flow. Mean delay from first negative ICP to TEVD was 1.8 days. All 8 patients demonstrated clinical improvement. TEVD resulted in improvement in Glasgow Coma Scale (mean increase 4.6, p = 0.003), and increases in ICP (mean increase 8.5, p < 0.001). Mean length of follow-up was 471.8 days. At follow-up, four patients had returned to pre-morbid functioning, three had a reduction in functioning attributable to their initial presentation (not NegPH), and one had died of unknown cause. Illustrative case descriptions are included. Conclusions: Negative-pressure hydrocephalus is a rare but underrecognised syndrome that can be successfully treated by timely external ventricular drainage titrated to maintain CSF flow, and subsequent low-pressure ventriculoperitoneal shunting. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Negative-pressure hydrocephalus (NegPH) is a rare condition that is characterised by enlarged ventricles and symptoms consistent with increased intracranial pressure in the setting of negative intracranial pressure (ICP). The first description of NegPH was provided by Vassilyadi et al., who reported 2 paediatric patients with
夽 Portions of this work were presented in an electronic presentation at the 81st Annual Scientific Meeting of the American Association of Neurological Surgeons, New Orleans, United States, April 27, 2013. ∗ Corresponding author at: School of Medicine, University of Tasmania, Private Bag 68, Hobart, Tasmania 7000, Australia. Tel.: +61 3 6226 2660; fax: +61 3 6226 4824. E-mail address: [email protected] (B.H.M. Hunn).
hydrocephalic symptoms, negative ICP, and clinical improvement with modification of cystopleural shunts to increase flow resistance [1]. Since this initial report, a total of five further cases have been reported in the literature, by Clarke and her colleagues, and Fillipidis et al. [2,3]. In 2006, Clarke et al. described two cases of likely NegPH treated with negative-pressure drainage of cerebrospinal fluid (CSF) and clinical response that was initially promising. Unfortunately, ultimate clinical outcome in both cases was poor; both patients were non-verbal at follow-up, one was bedridden and the other had been admitted to a residential care facility [2]. Notable in this series was a prolonged time from initial symptoms to ultimate treatment with external ventricular drainage. In 2011, Fillipidis et al. described a further 3 patients with low or negative-pressure hydrocephalus following surgical approaches to the cranial base [3]. Two of these patients improved with repair of CSF leaks and external ventricular drainage that was titrated to produce CSF
0303-8467/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2013.10.019
Please cite this article in press as: Hunn BHM, et al. Successful treatment of negative pressure hydrocephalus using timely titrated external ventricular drainage: a case series. Clin Neurol Neurosurg (2013), http://dx.doi.org/10.1016/j.clineuro.2013.10.019
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ARTICLE IN PRESS
Alive 63 8
Aneurysmal subarachnoid haemorrhage
70 7
M
F 54 6
F
M M 12 36 4 5
Aneurysmal subarachnoid haemorrhage Left MCA aneurysm, elective clipping
M F 51 65 2 3
Tectal plate cavernoma Metastatic adenocarcinoma of unknown origin Severe traumatic brain injury Severe traumatic brain injury
M 27 1
Pineal germinoma
Primary disease process Sex Age (y) Case number
Eight patients met the inclusion criteria, and relevant clinical details are summarised in Table 1. 5 were males. The teaching hospital from which these cases arose has a well-defined catchment population, which enabled estimation of the incidence of NegPH at 1 case per 380 250 people per year. The mean age at development of NegPH was 47.3 years (range 12–70 years, standard deviation (SD): 20.4 years). All patients had at least 1 preceding neurosurgical procedure, with the mean number of procedures 3.0 per patient (range 1–7, SD: 2.0). All patients were treated by external ventricular drainage that was titrated to maintain CSF flow volumes of between 5 and 15 mL per hour (titrated external ventricular drainage, TEVD), depending on clinical progress. This included negative-pressure drainage if this was required to maintain CSF flow. Negativepressure drainage was required in 6 cases. The mean time from first measured negative ICP to commencement of TEVD was 1.8 days (range 0–8 days, SD: 2.7 days). The mean duration of TEVD was 3.2 days (range 1–5 days, SD: 1.5 days). ICP prior to TEVD averaged −3.1 centimetres of water (cmH2 O) (range −1 to −7 cmH2 O, SD: 1.9 cmH2 O). Lowest recorded ICP averaged −6.5 cmH2 O (range −3 to −14 cmH2 O, SD: 1.9 cmH2 O). Average ICP following TEVD was 5.0 cmH2 O (range 2–7 cmH2 O, SD 1.9). The difference between ICP before and after TEVD was significantly different (mean increase 8.5 cmH2 O, p < 0.001). Mean GCS prior to TEVD was 9.4 (range 5–14, SD: 2.9). Following TEVD mean Glascow Coma Scale (GCS) was 14
Table 1 Characteristics of negative-pressure hydrocephalus patients.
3. Results
EVD, external ventricular drain; MCA, middle cerebral artery; VPS, ventriculoperitoneal shunt.
37 VPS with Medtronic Strata NSC valve set at 0.5
Dead 48 VPS with Medtronic Strata NSC valve set at 0.5
Alive 100 VPS with Medtronic Strata NSC valve set at 0.5
Alive Alive 345 200 VPS with Medtronic Strata II valve set at 1.0 VPS with Medtronic Strata NSC valve set at 0.5
Alive
Alive Alive 806 700 VPS with Medtronic Strata NSC valve set at 0.5 VPS with Medtronic Strata NSC valve set at 0.5
Definitive therapy
Length of follow-up (days)
Alive/dead
A retrospective audit of all neurosurgical cases occurring between 2006 and 2012 at a university teaching hospital was undertaken to identify cases of NegPH. Cases were drawn from the neurosurgical patient database. Cases were included if (i) a negative ICP was measured, (ii) there was concurrent radiographic evidence of ventriculomegaly, (iii) the patient was suffering symptoms that were attributable to hydrocephalus and coincided temporally with negative ICP and ventriculomegaly, and (iv) malfunction of the ICP monitor and other equipment had been excluded. ICP was monitored using strain gauge tipped intracranial catheters manufactured by Codman (Raynham, Massachusetts, USA), or via an external ventricular drain (EVD) (in all cases manufactured by Medtronic, Minneapolis, Minnesota, USA). EVDs were levelled to the tragus at the beginning of each nursing shift. Clinical parameters were monitored by trained neurosurgical nurses in a neurosurgical high dependency unit. Computed tomography (CT) scans were performed using a Siemens Somatom Definition AS scanner (Erlangen, Germany). Data was gathered on patients’ clinical parameters, including previous procedures, longitudinal data on ICPs, conscious state, treatment of NegPH, and outcome data. Statistical tests were performed using GraphPad Prism 6 (Graphpad Software, California, USA). Two-tailed paired t-tests were performed for continuous variables measured on each patient. A P value of less than 0.05 was used to determine significance.
1538
2. Materials and methods
VPS with Medtronic Strata II valve set at 0.5
Functional outcome
flow; both of these cases required drainage under subatmospheric pressures. Ultimately, one of these patients was provided with a ventriculoperitoneal shunt (VPS), and one was palliated due to poor progress. Their third case demonstrated clinical improvement solely with repair of a frontal CSF leak. In this paper we present the first series describing statistically significant clinical, manometric, and radiological improvement following treatment for NegPH, with data on long-term patient outcomes.
Returned to work and premorbid function CN VI palsy, balance difficulty Undergoing chemotherapy, balance difficulty Attending school with teaching aides Returned to premorbid function, mobilising with support Returned to work and premorbid function Discharged to an external hospital, died of unknown cause 48 days later Returned to work and premorbid function
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Fig. 1. Left: Change in ICP following TEVD. *p = 0.003, two-tailed paired t-test. Right: Change in GCS following TEVD. *p < 0.001, two-tailed paired t-test. GCS, Glasgow coma scale; ICP, intracranial pressure; TEVD, titrated external ventricular drainage.
(range 12–14, SD: 0.9). There was a statistically significant improvement in GCS following TEVD (mean increase 4.6, p = 0.003) (Fig. 1). Following cessation of TEVD, all patients underwent definitive treatment using low-pressure VPS. All shunts were fitted with programmable valves manufactured by Medtronic (Minneapolis, Minnesota, USA). No antisiphon devices were included in the shunt systems. 7 patients had valves programmed at setting 0.5 (approximately equivalent to 20 millimetres of water (mmH2 O)). Patient 4 had his valve set at 1.0 (approximately equivalent to 40 mmH2 O). The mean duration of follow-up was 471.8 days (range 37–1538, SD: 520.6). At follow-up 7 patients were alive. Patient 7 died 48 days following discharge to an external hospital, and no autopsy was performed to definitively ascertain cause of death. At followup 4 patients had regained their pre-morbid level of functioning. Of the remaining 3 surviving patients, all had sequelae that could be attributed to their primary disease process (Table 1).
4. Illustrative cases 4.1. Patient 3 A 65 year-old female was referred to our service with acute hydrocephalus of unknown aetiology and reduced conscious state (GCS 9) (Fig. 2A). There was no evidence on magnetic resonance studies of an obstructive lesion to account for the development of hydrocephalus. Lumbar puncture demonstrated increased CSF protein, but no other abnormalities. She underwent urgent insertion of an EVD; although pressures were initially elevated, after 2 h measured ICP ranged from 2 to −2 cmH2 O. Over the following 2 days there was minimal CSF drainage and no clinical improvement (Fig. 2B). On the third post-operative day the decision was made to titrate the height of drainage to maintain CSF flow volumes at 5 mL per hour, including drainage at subatmospheric pressures as required. This resulted in rapid improvement in conscious state, such that after drainage of 35 mL over seven hours the GCS was 14. Drainage continued under negative pressures for 5 days (Fig. 2C), following which a VPS was placed with a Medtronic Strata NSC Valve set at 0.5. Subsequent to her discharge it became apparent that her initial condition may have been due to cerebellar metastatic adenocarcinoma of unknown origin, and she underwent chemotherapy and subsequent surgical decompression of the cerebellum. At 23 months following titrated drainage and lowpressure VPS, there was no radiographic or clinical evidence of hydrocephalus recurrence (Fig. 2D).
4.2. Patient 8 A 63 year-old male suffered an aneurysmal subarachnoid haemorrhage (Hunt and Hess grade V) originating from an aneurysm of the anterior communicating artery, which was complicated by acute hydrocephalus (Fig. 2E). He was transferred to our with a GCS of 3, and underwent urgent insertion of an EVD, with drainage of 100 mL of blood-stained CSF over the following 12 h at a drainage height of 15 cm. On the following day he underwent craniotomy and clipping of the aneurysm. Post-operative digital subtraction angiography demonstrated a residual aneurysmal defect that was clipped on the third day following presentation. The patient continued to improve, such that on the twentieth day following presentation his GCS was 11, ICP had normalised, and the EVD was removed. In the 2 days following removal of the EVD the patient demonstrated a marked deterioration to a GCS of 8. CT of the brain showed marked dilatation of the ventricles, consistent with communicating hydrocephalus (Fig. 2F). Another EVD was subsequently inserted, and ICP measurements through this device were very low, between 0 and 5 cmH2 O. Negativepressure drainage was commenced over 24 h to maintain CSF drainage at 8 mL per hour. During this period GCS improved from 8 to 14 (Fig. 2G). 7 days after re-insertion of an EVD, a VPS was placed with a Medtronic programmable valve without an antisiphon device, with a valve setting of 0.5. He was subsequently discharged home, and one month following discharge had returned to work, and there was no further evidence of hydrocephalus (Fig. 2H).
5. Discussion 5.1. Pathogenesis of negative-pressure hydrocephalus Hydrocephalic states without elevated ICP first gained widespread recognition following the description by Adams and colleagues of what became known as normal-pressure hydrocephalus (NPH) [4]. NPH is characterised by pathological enlargement of the ventricles with normal opening pressures on lumbar puncture, and a triad of clinical symptoms that include dementia, gait ataxia, and urinary incontinence [4]. Adams et al. demonstrated resolution of dementia in a significant proportion of their study population following ventriculoperitoneal shunting of CSF [4]. Further studies demonstrated the utility of refined patient selection to better target ventriculoperitoneal shunting to those
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Fig. 2. (A–D) Patient 3, a 65 year-old female who presented with acute hydrocephalus. (E–H) Patient 8, a 63 year-old male who presented following an aneurysmal subarachnoid haemorrhage. (A and E) CT scan at initial presentation. (B and F) CT scans demonstrating ventriculomegaly associated with NegPH. (C and G) CT scans following TEVD. (D and H) CT scans at last follow-up (described in Table 1). NegPH, negative-pressure hydrocephalus; TEVD, titrated external ventricular drainage.
patients with true NPH, rather than conditions with similar symptoms such as vascular dementia or Alzheimer’s disease [5–7]. The pathogenic alterations underlying NPH and its symptomatology have been extensively researched since its original description. Key features thought to underlie the NPH disease process include ongoing “high-normal” CSF pressures, white matter changes, and alterations to cerebral blood flow [8–10]. Interestingly, it has recently been demonstrated that clinical improvement in NPH, at least with CSF drainage via lumbar puncture, does not correlate with change in ventricular size [11]. This may indicate that clinical improvement in NPH is due to reduction of total brain water and alterations in brain compliance and homeostasis, rather than change in ventricular size. More recently, the literature has described multiple cases of low-pressure hydrocephalus (LPH). LPH was first described by Pang & Altschuler in 1994, in 12 children who had initially undergone medium-pressure ventriculoperitoneal shunting for treatment of hydrocephalus [12]. All twelve children presented with a hydrocephalic syndrome, in the setting of low intracranial pressures. Resolution of symptoms occurred following drainage of CSF under subatmospheric pressures. Since Pang & Altschuler’s initial report, several other authors have described cases of low-pressure hydrocephalus [13–15]. Multiple mechanisms have been suggested for the pathogenesis of LPH. In their early work on the subject, Pang & Altschuler described their theory of alterations in the viscoelastic modulus of the brain, mediated by reduced brain extracellular fluid content secondary to prolonged overstretching of the brain parenchyma. In this hypothesis, distortion of brain tissue results in symptoms by way of cortical ischaemia and elevated compressive stresses within the brain [12]. Although this hypothesis has not been tested in LPH, reduction in cerebral blood flow is known to occur in NPH, and has been demonstrated to normalise following CSF drainage and resolution of ventriculomegaly [9,16]. In 2002, Lesniak et al. enlarged on the work of Pang & Altschuler, using the concept of elastic hysteresis to demonstrate that when brain compliance is altered, ventriculomegaly can persist at an intracranial pressure that would previously have resulted in normal ventricular volume [14]. Virtual simulations have also emphasised the role brain turgor has in the pathogenesis of inappropriately low-pressure hydrocephalus [17]. Treatment of LPH has been investigated by Hamilton
& Price, who found that endoscopic third ventriculostomy was beneficial in reducing the number of patients requiring a permanent VPS [18]. In some of the only work published regarding NegPH, Fillipidis and colleagues suggest that CSF leaks play a pivotal role in the development of a negative-pressure hydrocephalic state, by producing a very-low subarachnoid pressure [3]. Very-low subarachnoid pressures in turn produce a transmantle pressure gradient that generates a state in which ventriculomegaly can persist with negative ICP. The initial cause of ventriculomegaly may be a blockage between the ventricles and the subarachnoid space, possibly caused by haemorrhage into the CSF. These hypotheses are supported by the fact that every reported case of NegPH, including our series, features a prior surgical operation disrupting pressure homeostasis, and therefore also a potential source of haemorrhage, however minor. Furthermore, the fundamental importance of cortical subarachnoid space disruption in the development of lowpressure hydrocephalic states has been emphasised by computer modelling [19]. It is possible that several aetiologic mechanisms are at play in NegPH; CSF leaks and blood products within the CSF precipitate ventriculomegaly, and associated with this brain water and compliance are altered. This creates a state in which ventriculomegaly can persist with negative ICP. Changes in neuronal homeostasis and cerebral blood flow may manifest as the clinical presentation described in our patients. TEVD is therefore required in order to “reset” parenchymal compliance to its normal state, in accordance with the theory of elastic hysteresis provided by Lesniak et al. in regards to LPH [14]. NegPH likely lies on one extreme of a continuum of pressure–volume relationships within the cranial vault, with prototypical cases of acute hydrocephalus that adhere to the Monro-Kellie doctrine at the other extreme. NPH and LPH occupy the spectrum between these two extremes. More cases of NegPH are required before definitive statements regarding the pathogenesis of this disease can be made. Indeed, the true pathogenesis of NegPH is likely to remain obscure until the nature of physiological CSF production has been fully elucidated. Current evidence suggests that CSF production and metabolism is much more dynamic and geographically diverse than traditionally taught [20,21].
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5.2. Suggested clinical approach In all cases where a patient’s neurological state deteriorates, and there is clinical suspicion of hydrocephalus, imaging should be performed to confirm the diagnosis. Subsequent EVD insertion and pressure monitoring should proceed if this is clinically appropriate. In those cases where there are positive ICPs and CSF drainage is adequate, standard care should follow. In the very small minority of cases where negative ICPs exist or develop, there is impairment of CSF drainage, and persistent ventriculomegaly, the patient should be admitted to a neurosurgical high-dependency unit for intensive monitoring of neurological state and ICPs. The draining pressure of the EVD should be titrated to achieve 5–10 mL per hour of CSF drainage. If clinical and manometric improvement does not follow, it may be necessary to re-titrate to higher drainage targets. The focus should be on targeted drainage volume, rather than targeted ICP. The key concern in treating a patient with TEVD is that low or negative pressures may be required to produce CSF flow, and that this may cause subdural effusion. This risk needs to be balanced against the potential benefit of TEVD in each patient. Following clinical and manometric resolution of NegPH, some degree of ventriculomegaly may persist, associated with relatively low ICPs. Essentially, a low-pressure hydrocephalic state has now been created. In this series we have described successful treatment using low-pressure ventriculoperitoneal shunting as the final therapy in resolving NegPH. 6. Conclusion In this case series we present the first data demonstrating successful long-term treatment of patients suffering from NegPH. The critical points illustrated by our work are the importance of early recognition and prompt treatment of NegPH. Future research should aim to provide evidence to cement or disprove the proposed treatment regime, and also to describe etiologic factors for NegPH, such that it may be prevented. Acknowledgements The authors would like to thank their colleagues for support and critical appraisal of methods and manuscripts. References
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