User Tools

Site Tools


idiopathic_normal_pressure_hydrocephalus

Idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurodegenerative disease in the elderly with enlarged ventricles and normal or slightly elevated cerebrospinal fluid pressure, clinically characterized by an insidious onset and gradual progression of impairments of gait, balance, cognition, with urinary incontinence 1).

History

Normal Pressure Hydrocephalus first became recognized on March 10, 1964 as a distinct medical syndrome by Salomón Hakim, M.D., Ph.D.

The classic triad of magnetic apraxia, urinary incontinence, and dementia remain relevant into the 21(st) century as being the basis for symptomatic diagnosis and predicting potential benefit from cerebrospinal fluid shunting, though they have been greatly augmented by the addition of modern neuroimaging, particularly MRI.

Modern criteria recognize a wider range of diagnostic criteria, and new positive and negative prognostic indicators for treatment benefit have been discovered, though the mainstay remains initial drainage of a large volume of cerebrospinal fluid and monitoring for clinical improvement. Even with our advances in understanding both primary and secondary normal pressure hydrocephalus, diagnosis, management, and counseling remain challenging in this disorder 2).

Epidemiology

iNPH appears to be extremely under-diagnosed. Properly designed and adequately powered population based studies are required to accurately characterize this disease's epidemiology 3).

It is predominantly a disease of the elderly. By its nature, many of those who present to clinic are in advanced old age with multiple comorbidities. Majority of patients treated are younger than 80 years old.

It occurs most frequently in the 70s, gait impairment and cognitive decline are the most frequent initial symptoms in men and women, respectively, and hypertension and diabetes are the most frequent comorbidities in men and women, respectively 4).


In people over 65 years old, pooled prevalence obtained from specific population studies was 1.3%, almost 50-fold higher than that inferred from door-to-door surveys of dementia or Parkinsonism. Prevalence may be even higher in assisted-living and extended-care residents, with up to 11.6% of patients fulfilling the criteria for suspected iNPH and 2.0% of patients showing permanent improvement after cerebrospinal fluid (CSF) diversion. The only prospective population-based survey that reported iNPH incidence estimated 1.20 cases/1000 inhabitants/year, 15-fold higher than estimates obtained from studies based on hospital catchment areas. The incidence of shunt surgery for iNPH and SRiNPH obtained from incident cases of hospital catchment areas appears to be fewer than two cases and one case/100,000 inhabitants/year, respectively. Unfortunately, there is no population-based study reporting the real values for these two parameters.

The prevalence of iNPH, in Japan among people older than 65, the prevalence is between 0.5% and 2.9% 5) and the syndrome is both underdiagnosed and undertreated.

Classification

It is recommended that INPH be classified into probable, possible, and unlikely categories. It is hope that these criteria will be widely applied in clinical practice and will promote greater consistency in patient selection in future clinical investigations involving INPH 6).

Etiology

Unknown.

All patients with idiopathic normal pressure hydrocephalus (INPH) who underwent shunting in Sweden in 2008-2010 were compared to age- and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important vascular risk factor (VRFs) and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity.

In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%.

The findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH 7).

Pathogenesis

Although the exact pathogenesis of NPH is unknown, many possible causes have been postulated, including cerebral ischemia. Studies have demonstrated that periventricular blood flow and cerebrovascular autoregulation are reduced.

It is also thought that biomechanical changes, such as the combination of tissue distortion caused by ventricular dilation, CSF and interstitial fluid stasis, and impaired autoregulation may result in failure of drainage of neurotoxic compounds such as Amyloid beta.

Increased CSF stroke volume through the aqueduct has also been demonstrated in the NPH population despite normal CSF pressures. The reaction of the cerebral mantle to all or some of these processes is poorly understood. It is thought that white matter tract connections serving the cortex could be disrupted in a variety of ways, including disconnection, swelling, stretching, and compression. Therefore, it is possible that some types of disruption may be more tolerable (i.e., more reversible) than others.

Only a few studies have seized the opportunity to reevaluate the theories of pathogenesis of NPH using developments in imaging techniques.


The disorders of Alzheimer disease, vascular dementia and normal pressure hydrocephalus are all causes of dementia in the elderly population. It is often the case that it is clinically very difficult to tell these diseases apart. All three forms of dementia share the same risk factors, which for the most part are vascular risk factors. Bateman proposes that there is an underlying vascular pathophysiology behind these conditions, which is related to the strength of the pulse waves induced in the craniospinal cavity by the arterial vascular tree. It is proposed the manifestation of the dementia in any one patient is dependant on the way that the pulsations interact with the brain and its venous and perivascular drainage. This interaction is predominately dependant on the compliance of the craniospinal cavity and the chronicity of the increased pulse wave stress 8).


Experimental animal model

Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed.

Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement.

Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus 9).

Pathophysiology

Disturbed cerebrospinal fluid (CSF) dynamics are part of the pathophysiology of normal pressure hydrocephalus (NPH).

A study investigated the contribution of established CSF dynamic parameters to mean pulse amplitude (AMP), a prognostic variable defined as mean amplitude of cardiac-related intracranial pressure pulsations during 10 min of lumbar infusion test, with the aim of clarifying the physiological interpretation of the variable. AMP(mean) and CSF dynamic parameters were determined from infusion tests performed on 18 patients with suspected NPH. Using a mathematical model of CSF dynamics, an expression for AMP(mean) was derived and the influence of the different parameters was assessed. There was high correlation between modelled and measured AMP(mean) (r = 0.98, p < 0.01). Outflow resistance and three parameters relating to compliance were identified from the model. Correlation analysis of patient data confirmed the effect of the parameters on AMP(mean) (Spearman's ρ = 0.58-0.88, p < 0.05). Simulated variations of ±1 standard deviation (SD) of the parameters resulted in AMP(mean) changes of 0.6-2.9 SD, with the elastance coefficient showing the strongest influence. Parameters relating to compliance showed the largest contribution to AMP(mean), which supports the importance of the compliance aspect of CSF dynamics for the understanding of the pathophysiology of NPH 10).

Clinical Features

Elderly presenting with gait abnormality, cognitive decline, and urinary incontinence, with enlarged ventricles of the brain but normal or slightly elevated cerebrospinal fluid (CSF) pressure 11) 12).

Postural stability in NPH is predominantly affected by deficient vestibular functions, which did not improve after spinal tap test. Conditions which improved best were mainly independent from visual control and are based on proprioceptive functions 13).

The natural course of iNPH is symptom progression over time, with worsening in gait, balance and cognitive symptoms. This deterioration is only partially reversible.

Currently there is no pathological hallmark for iNPH 14).

It is frequently present with cerebral vasculopathy; significantly increased prevalence of cardiovascular disease iNPH patients, which provide evidence that cardiovascular disease is involved as an exposure in the development of iNPH 15).

Idiopathic normal pressure hydrocephalus (iNPH) may present, besides the classic triad of symptoms, extrapiramidal parkinsonian like movement disorders.

Scales

Diagnosis

Differential diagnosis

Treatment

Management of idiopathic normal-pressure hydrocephalus (iNPH) is hard because the diagnosis is difficult and shunt surgery has high complication rates. .

Shunt surgery has been established as the only durable and effective treatment for idiopathic normal pressure hydrocephalus

To maximise the benefits of shunt treatment, surgery should be performed soon after diagnosis 16).

The results of a prospective multicentre study on patients with iNPH diagnosed solely on clinical and radiological criteria support shunt surgery in patients presenting with symptoms and signs and MRI findings suggestive of iNPH 17).

Shunt

Endoscopic third ventriculostomy

The only randomized trial of endoscopic third ventriculostomy (ETV) for idiopathic normal pressure hydrocephalus (iNPH) compares it to an intervention which is not a standard practice (VP shunting using a non-programmable valve). The evidence from this study is inconclusive and of very low quality. Clinicians should be aware of the limitations of the evidence. There is a need for more robust research on this topic to be able to determine the effectiveness of ETV in patients with iNPH 18).

Outcome

Complications

Subdural collections, shunt malfunction, and postoperative seizures constituted the most frequent complications 19).

see Shunt overdrainage in idiopathic normal pressure hydrocephalus.

Case series

1)
Hakim S, Adams RD. The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci. 1965 Jul-Aug;2(4):307-27. PubMed PMID: 5889177.
2)
Finney GR. Normal pressure hydrocephalus. Int Rev Neurobiol. 2009;84:263-81. doi: 10.1016/S0074-7742(09)00414-0. Review. PubMed PMID: 19501723.
3)
Martín-Láez R, Caballero-Arzapalo H, López-Menéndez LÁ, Arango-Lasprilla JC, Vázquez-Barquero A. Epidemiology of Idiopathic Normal Pressure Hydrocephalus: A Systematic Review of the Literature. World Neurosurg. 2015 Jul 13. pii: S1878-8750(15)00871-2. doi: 10.1016/j.wneu.2015.07.005. [Epub ahead of print] Review. PubMed PMID: 26183137.
4)
Kuriyama N, Miyajima M, Nakajima M, Kurosawa M, Fukushima W, Watanabe Y, Ozaki E, Hirota Y, Tamakoshi A, Mori E, Kato T, Tokuda T, Urae A, Arai H. Nationwide hospital-based survey of idiopathic normal pressure hydrocephalus in Japan: Epidemiological and clinical characteristics. Brain Behav. 2017 Jan 27;7(3):e00635. doi: 10.1002/brb3.635. eCollection 2017 Jan 27. PubMed PMID: 28293475; PubMed Central PMCID: PMC5346522.
5)
Iseki C, Kawanami T, Nagasawa H, Wada M, Koyama S, Kikuchi K, Arawaka S, Kurita K, Daimon M, Mori E, Kato T. Asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus on MRI (AVIM) in the elderly: a prospective study in a Japanese population. J Neurol Sci. 2009 Feb 15;277(1-2):54-7. doi: 10.1016/j.jns.2008.10.004. Epub 2008 Nov 5. PubMed PMID: 18990411.
6)
Relkin N, Marmarou A, Klinge P, Bergsneider M, Black PM. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005 Sep;57(3 Suppl):S4-16; discussion ii-v. Review. PubMed PMID: 16160425.
7)
Israelsson H, Carlberg B, Wikkelsö C, Laurell K, Kahlon B, Leijon G, Eklund A, Malm J. Vascular risk factors in INPH: A prospective case-control study (the INPH-CRasH study). Neurology. 2017 Jan 6. pii: 10.1212/WNL.0000000000003583. doi: 10.1212/WNL.0000000000003583. [Epub ahead of print] PubMed PMID: 28062721.
8)
Bateman GA. Pulse wave encephalopathy: a spectrum hypothesis incorporating Alzheimer's disease, vascular dementia and normal pressure hydrocephalus. Med Hypotheses. 2004;62(2):182-7. PubMed PMID: 14962623.
9)
Jusué-Torres I, Jeon LH, Sankey EW, Lu J, Vivas-Buitrago T, Crawford JA, Pletnikov MV, Xu J, Blitz A, Herzka DA, Crain B, Hulbert A, Guerrero-Cazares H, Gonzalez-Perez O, McAllister JP 2nd, Quiñones-Hinojosa A, Rigamonti D. A Novel Experimental Animal Model of Adult Chronic Hydrocephalus. Neurosurgery. 2016 Nov;79(5):746-756. PubMed PMID: 27759679.
10)
Qvarlander S, Malm J, Eklund A. CSF dynamic analysis of a predictive pulsatility-based infusion test for normal pressure hydrocephalus. Med Biol Eng Comput. 2014 Jan;52(1):75-85. doi: 10.1007/s11517-013-1110-1. Epub 2013 Oct 23. PubMed PMID: 24151060.
11)
Hakim S, Adams RD (1965) The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure. Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci 2: 307–327.
12)
Adams RD, Fischer CM, Hakim S, Ojemann RG, Sweet WH (1965) Symptomatic occult hydrocephalus with “normal” cerebrospinal-fluid pressure. A treatable syndrome. N Engl J Med 273: 117–126.
13)
Abram K, Bohne S, Bublak P, Karvouniari P, Klingner CM, Witte OW, Guntinas-Lichius O, Axer H. The Effect of Spinal Tap Test on Different Sensory Modalities of Postural Stability in Idiopathic Normal Pressure Hydrocephalus. Dement Geriatr Cogn Dis Extra. 2016 Sep 27;6(3):447-457. PubMed PMID: 27790243; PubMed Central PMCID: PMC5075737.
14)
Leinonen V, Koivisto AM, Savolainen S, Rummukainen J, Sutela A, et al. (2012) Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature. Neuropathol Appl Neurobiol 38: 72–86.
15)
Eide PK, Pripp AH. Increased prevalence of cardiovascular disease in idiopathic normal pressure hydrocephalus patients compared to a population-based cohort from the HUNT3 survey. Fluids Barriers CNS. 2014 Aug 19;11:19. doi: 10.1186/2045-8118-11-19. eCollection 2014. PubMed PMID: 25180074; PubMed Central PMCID: PMC4150119.
16)
Andrén K, Wikkelsø C, Tisell M, Hellström P. Natural course of idiopathic normal pressure hydrocephalus. J Neurol Neurosurg Psychiatry. 2013 Nov 29. doi: 10.1136/jnnp-2013-306117. [Epub ahead of print] PubMed PMID: 24292998.
17)
Klinge P, Hellström P, Tans J, Wikkelsø C; European iNPH Multicentre Study Group. One-year outcome in the European multicentre study on iNPH. Acta Neurol Scand. 2012 Sep;126(3):145-53. doi: 10.1111/j.1600-0404.2012.01676.x. Epub 2012 May 10. PubMed PMID: 22571428.
18)
Tudor KI, Tudor M, McCleery J, Car J. Endoscopic third ventriculostomy (ETV) for idiopathic normal pressure hydrocephalus (iNPH). Cochrane Database Syst Rev. 2015 Jul 29;7:CD010033. doi: 10.1002/14651858.CD010033.pub2. Review. PubMed PMID: 26222251.
19)
Black PM. Idiopathic normal-pressure hydrocephalus. Results of shunting in 62 patients. J Neurosurg. 1980 Mar;52(3):371-7. PubMed PMID: 7359191.
idiopathic_normal_pressure_hydrocephalus.txt · Last modified: 2018/01/29 13:39 by administrador