Normal Pressure Hydrocephalus

Normal Pressure Hydrocephalus Fifteen–Twenty High-Yield Points Definition and historical background

NPH is an adult-onset chronic condition with enlarged cerebral ventricles on imaging plus the clinical Hakim and Adams triad — gait disturbance, cognitive decline and urinary incontinence — occurring without high CSF pressure or obstruction to flow through the ventricular system and subarachnoid space.

It is a potentially reversible neurological disease, but the mechanisms are unclear and awareness is poor, leading to under-recognition and undertreatment. In older people the triad overlaps other age-related diseases and may be wrongly attributed to ageing itself as a result of ageism.

Hakim and Adams recognised the syndrome in 1957 and published it in 1965, linking the triad definitively to CSF accumulation in the ventricles and showing improvement after lumbar puncture and shunt diversion. Evans' ratio was described in 1942 following the introduction of air ventriculography in 1918.

Crude prevalence is 10–22/100,000 for probable NPH and 29/100,000 for possible NPH. Age-specific rates rise from 3.3/100,000 at age 50–59 to 5.9% in those aged 80 and above. Incidence rises from 0.07/100,000/year under 60 to 1.2/1,000/year over 70. In nursing homes, incidence rates are 9–14% depending on the criteria used.

Symptoms do not result simply from impaired CSF dynamics. The interacting mechanisms are altered CSF dynamics and impaired resorption, reduced intracranial compliance, abnormal cerebral perfusion with periventricular ischaemia, altered metabolism, oedema and demyelination, and accumulation of neurotoxic substances — together producing "cerebral dyshomeostasis".

Recognised associations include cardiac systolic dysfunction and obstructive sleep apnoea, which is frequently co-existent and should be actively sought.

Gait disturbance is the earliest and most prominent symptom — wide-based, slow, unsteady and magnetic, with disturbed tandem walking and turning, small steps, reduced floor foot clearance, start hesitation, tendency to fall and disturbed trunk balance. The Dutch NPH study quantified this as 25 steps and 16 seconds for a 10-metre walk versus 15 steps and 8 seconds in controls.

Cognition shows an atypical profile combining frontal-executive, subcortical and posterior cortical impairment. Memory and orientation are relatively preserved; frontal impairment affects recall disproportionately to recognition, with attention deficit and reduced psychomotor speed. In Alzheimer's disease the temporal-lobe profile impairs both recall and recognition — the key clinical contrast.

Urinary symptoms begin as frequency and urgency and progress to urge and then complete incontinence as frontal deterioration prevents recognition of the urge. Mechanisms are reduced bladder capacity (mean 200 mL), detrusor overactivity and enhanced parasympathetic activity, reversible after LP and shunting. Faecal incontinence occurs only in advanced stages.

Severity is graded using the iNPH Grading Scale (iNPHGS), which scores gait, cognition and urinary function from 0 to 4 each.

Must be distinguished from Alzheimer's disease, frontotemporal degeneration and vascular cognitive impairment; Parkinson's disease, vascular parkinsonism and Parkinson-plus syndromes; primary progressive freezing gait; and lumbar canal stenosis. NPH gait does not respond to external cues or to levodopa, unlike Parkinson's disease, and there is no tremor or rigidity.

Imaging features: ventricular enlargement not entirely attributable to atrophy (Evans' index >0.3), no macroscopic obstruction to CSF flow, an aqueductal or fourth ventricular flow void on MRI, plus at least one of — enlarged temporal horns, callosal angle of 90 degrees or less, or altered brain water content not attributable to microvascular ischaemia or demyelination.

DESH — disproportionately enlarged subarachnoid space hydrocephalus, i.e. narrowed sulci and subarachnoid spaces over the high convexity and midline with dilated Sylvian fissures — is stressed by the revised 2012 Japanese criteria as a very important diagnostic criterion, which can only be overcome by evidence of improvement after a CSF tap or drainage test.

American guidelines (Relkin, Marmarou et al.) classify NPH as probable, possible or unlikely. Supporting history: insidious onset after age 40, duration of at least 3–6 months, progression over time, no antecedent cause of secondary hydrocephalus, and no alternative explanation. Gait/balance disturbance must be present plus impairment of cognition, urinary function or both. Probable NPH requires an opening pressure of 5–18 mmHg (70–245 mm H2O); higher or lower pressures are inconsistent with the diagnosis.

Japanese criteria: possible iNPH — onset in the 60s or later, more than one triad element, Evans' index >0.3, no other explanation, and no obvious antecedent cause; probable — adds CSF pressure of 200 mm H2O or less with normal content, plus either DESH, or improvement after the CSF tap test, or improvement after the drainage test; definite iNPH — improvement of symptoms after the shunt procedure.

CSF tap test (high-volume LP): walking speed is assessed in single-task and dual-task conditions, with maximal improvement 24–48 hours after LP for single-task tests and 48–72 hours for dual-task tests, returning to the pre-LP state after a few weeks, which further supports the diagnosis. Sensitivity is low (26–61%), so a negative tap test cannot exclude NPH; a positive test carries greater certainty of shunt response than clinical examination alone.

Extended lumbar drainage (ELD): a lumbar catheter draining 100–150 mL of CSF per day for about four days, with daily assessment of gait and cognition. Sensitivity 50–100% and positive predictive value 80–100%, better than LP alone, but a negative result has deceptively low value because of frequent false negatives. Discontinue for low-pressure headache, nerve root irritation or signs of meningitis. Prior stroke predicts a worse outcome; DESH predicts a better one.

CSF outflow resistance (Ro) by infusion test has sensitivity 57–100% and PPV 75–92%. Static ICP measurement does not predict surgical outcome — it is ICP pulsatility and B-waves (slow rhythmic oscillations at 0.33–3 cycles/minute) that carry clinical significance, indicating reduced intracranial compliance.

CSF biomarkers: a decrease in A-beta-42 is seen in both NPH and Alzheimer's disease, but a rise in phospho-tau is seen only in Alzheimer's — useful for differential diagnosis, although no CSF test has prognostic value before shunting.

CSF diversion is the only evidence-based curative treatment; repeated high-volume lumbar punctures have no long-term efficacy in non-operated patients. Ventriculoperitoneal shunting is standard care and succeeds in about 80% of cases. Improvement is greatest for gait (81–86%) and bladder control (70%) and least consistent for cognition (40–44%); there is a 96% chance of subjective improvement and 83% chance of improvement on timed walk at six months, against a serious adverse event risk of about 11%. Age is not a prognostic factor. Complications include shunt infection (a neurosurgical emergency), subdural effusion (managed by raising the setting of an adjustable valve), obstruction, catheter fracture and transient hearing loss; ventricles do not necessarily shrink after successful shunting. Endoscopic third ventriculostomy avoids shunt hardware but may fail if the stoma closes.