Reversible long-standing severe disability in idiopathic normal pressure hydrocephalus

Practical Implications

Idiopathic normal pressure hydrocephalus patients with severe and prolonged disability may benefit from shunting if there is an objective response to tap or drainage tests.

Idiopathic normal pressure hydrocephalus (iNPH) presents with the triad of impaired gait, impaired cognition, and urinary incontinence, with enlarged ventricles and normal CSF pressure.¹ Reports of CSF shunting and outcome after prolonged severe disability are few. We report a patient who responded dramatically to shunting despite severe motor and cognitive impairment and incontinence for more than a year.

Case report

A 71-year-old man with long-standing obsessive-compulsive disorder (OCD) developed hypomania with elevated mood, insomnia, and grandiosity at age 68. After responding to quetiapine, escitalopram and galantamine were added for OCD and “mixed dementia.” The latter diagnosis appears to have been based on functional decline and ischemic changes on brain CT, although this was not confirmed on subsequent MRI. One year later, he developed mania and improved with valproic acid and olanzapine, which replaced quetiapine. Walking became progressively slower with multiple falls. Despite discontinuation of olanzapine, he became nonambulatory. A levodopa trial produced visual hallucinations. Over the following year, he developed forgetfulness, apathy, disinhibition, multitasking difficulties, poor judgment, and double incontinence. He had hypertension, diabetes, hypercholesterolemia, and coronary artery disease. There was no family history of psychiatric disorders or dementia.

On admission to the hospital, he was alert and anxious. Insight was poor for cognitive problems but fair for motor disability. Medications included donepezil and valproic acid. Mini-Mental State Examination (MMSE) score was 5/30. Examination showed slowed saccadic eye movements, cogwheel rigidity, bradykinesia, upper limb postural tremors, and profound lower limb stiffness. He could not stand or sit unsupported. Deep tendon reflexes were grade 2 bilaterally. Plantar responses were flexor. Valproic acid was discontinued to rule out drug-induced parkinsonism. The patient did not improve.

Diagnosis and investigations

Head CTs performed 2 years apart and brain MRI showed increasing diffuse ventricular enlargement, periventricular transependymal exudates, and mild cortical atrophy. Brain SPECT showed mildly reduced right temporal perfusion. Lumbar tap test was performed. Thirty mL of CSF was removed with difficulty in sitting position. Flow was so slow that pressure could not be measured reliably. Cell count, protein, and glucose were normal. Pre/post tap test mobility, motor speed, and neuropsychology assessments are shown in tables 1 and 2. He could not complete formal cognitive testing due to severe cognitive impairment. Within 24 hours after lumbar tap, he showed major improvement in sitting balance, with easier transfers and gradual improvement in motor speed over the next 6 weeks. Diagnosis of probable iNPH was considered.²

Table 1.

Physiotherapy and motor speed assessments

Table 2.

Neuropsychology assessment

Shunting

Right frontal Medtronic Strata II valve ventriculoperitoneal shunt set at 1.5 was inserted. Frontal biopsy showed normal brain. Ten weeks post shunt, he required less assistance with gross motor function and ambulation. Cognitively he was testable but still severely impaired. Cognitive profile and behavioral observations suggested frontal-subcortical deficits, with relative sparing of information retention and visuospatial functioning. After shunt level was adjusted to 1, further motor and cognitive improvement occurred.

Five-month postoperative assessment showed mild hypertonia and normal muscle power, sensation, and coordination. He walked independently with a device and showed steady improvement in gait speed, step length, and distance (video at Neurology.org/cp). Incontinence resolved. MMSE score was 27/30. Behavioural Neurology Assessment-Short Form³ score was 78/114, whereas he was not testable preoperatively (cutoff for dementia is 82). Mild hypomanic symptoms emerged and improved with lithium.

DISCUSSION

Our patient with severe motor, sphincter, and cognitive impairment for more than a year showed clear improvement after a tap test and then marked improvement after ventriculoperitoneal shunt insertion. This confirmed definite iNPH.² Drug-induced parkinsonism was ruled out by absence of improvement following olanzapine and valproic acid discontinuation. Parkinson disease and Alzheimer disease are unlikely due to absence of levodopa response, normal brain biopsy, prominent response to shunting, and neuroimaging results. MRI did not support vascular dementia. Although mania has been described in 2 symptomatic NPH cases, postmeningitic⁴ and posttraumatic,⁵ this iNPH case started with hypomania.

Poca et al.⁶ reported predictive factors associated with unfavorable outcome in NPH: idiopathic form, prolonged duration (>12 months), dementia (MMSE < 24), cerebral atrophy, incomplete clinical triad, absence of periventricular lucencies, and age over 64 years. However, they reported good shunt results in 12 patients with iNPH despite 4 poor prognostic factors in each. Our patient had 4 of these factors; compared with their patients, he had the lowest MMSE score and severely impaired gait and sphincter function. Nevertheless, outcome was excellent. A review of 44 published studies on treatment of NPH⁷ concluded that there is no reliable way to predict which patients will improve. iNPH patients with severe and prolonged disability may still benefit from shunting if there is an objective response to tap or drainage tests.

STUDY FUNDING

No targeted funding reported.

DISCLOSURES

A.M. Selim reports no disclosures. C. Ray received speaker honoraria from an Ontario Long-Term Care Physician Conference. M.D. Cusimano has received research support from the Canadian Institutes of Health Research and the Ontario Neurotrauma Foundation. E. Karp reports no disclosures. M. Freedman received honoraria from Bristol Myers Squibb for attending a consultancy meeting; received financial support for a Behavioural Neurology fellow from Eli Lilly Canada; receives publishing royalties for Clock-drawing: A Neuropsychological Analysis (Oxford University Press, 1994); is listed on a provisional patent related to methods and kits for differential diagnosis of Alzheimer disease vs frontotemporal dementia using blood biomarkers and may be listed on the planned patent application; serves on the editorial board of Brain and Cognition; receives funding from the Brain Canada: Multi-Investigator Research Initiative, Canadian Institutes of Health Research, Ontario Neurodegenerative Disease Research Initiative, and Academic Health Science Centre (Alternate Funding Plan Grant); has received funding from the Parkinson Society of Canada; and receives support from the Saul A. Silverman Family Foundation as a Canada International Scientific Exchange Program and Morris Kerzner Memorial Fund. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.