To the Editor: We present a case of a patient with classical symptoms of normal-pressure hydrocephalus (NPH), as well as abulia, that evolved into severe agitation after large-volume lumbar puncture, and we review the literature on neuropsychiatric symptoms in NPH.
A 64-year-old man presented to a local emergency department with confusion, gait impairment, and urinary incontinence. He had a history of depression treated with citalopram 60 mg daily for 9 years and methylphenidate 20 mg tid since the late 1990s. His past medical history consisted of hypertension, obstructive sleep apnea, coronary artery disease, and alcohol dependence in remission for over 6 years. Two days before admission, he was jailed for driving on a suspended license, and released from the police station on the day of admission. He did not receive his usual medications during that time. Patrolmen found the patient several hours later standing in the same spot in front of the station, with word-finding difficulties, problems ambulating, and urinary incontinence, and brought him to the local emergency department.
His vital signs on presentation were temperature 36.5°C, heart rate 116, blood pressure 133/69, respiration rate 22, O2 94% on room air. On examination, the patient was alert, with an intense staring gaze, speech latency, and intermittent jerking of his head and limbs. Cranial nerves, sensory, strength, and reflex examination were normal, but the patient was unable to lift his feet more than one inch off the ground and had a severe shuffling gait. He repeatedly said the phrase, “Start over; go back to the beginning, and you’ll see,” and perseverated about “the 12th step of Alcoholics Anonymous.”
Laboratory studies were notable for white blood cell count 11.0, hematocrit 30%, platelets: 291. Electrolytes were normal with the exception of mildly elevated blood urea nitrogen of 48 mmol/L and creatinine 1.60. Blood glucose was 137. ALT was 45, AST 84, alkaline phosphatase 73, and total bilirubin 0.6. NH3 was 37. TSH was 0.751. Treponema pallidum antibody was negative. B12 and folate were within normal limits. Serum iron was low at 24, and creatine kinase was elevated at 2,978. Urinalysis and toxicologic screen were negative. Computed tomography scan of the brain revealed severe white-matter changes, with possible transependymal flow, old lacunar infarctions in the right basal ganglia and internal capsule, and prominence of the ventricular system in both temporal and frontal horns out of proportion to sulcal widening.
The patient was sedated with 1 mg of midazolam, and a lumbar puncture (LP) was performed, which demonstrated 1 red blood cell, 1 white blood cell, glucose 57, total protein 54, and an opening pressure of 21 cm of water (normal: <25). Thirty-six milliliters of cerebrospinal fluid (CSF) were aspirated during the procedure. CSF culture was negative for organisms, and HSV PCR was negative.
When the patient awoke 20 minutes later, he had noticeably improved gait, interactivity, and continence. However, over the course of the next 12 hours, he manifested increasing agitation, with elevated heart rate and blood pressure and insomnia, with no response to 5 mg of intravenous haloperidol. Psychiatric consultation was requested, and, on evaluation, he was found dancing in his bed, groping the air with his hands, impulsively trying to leave the room, repeatedly slapping his leg with his hand, repeating the phrase “I’m a flying medical missionary.”
Physical examination revealed grasp reflexes in both hands, but otherwise no focal neurological deficits. He then received 4 mg of intravenous lorazepam over the course of 2 hours and slept for the remainder of the day. The next morning he was calm, lucid, speaking and behaving normally, and with normal vital signs. Electroencephalogram (EEG) revealed a normal posterior background rhythm of 9 Hz without epileptiform abnormalities. MRI of the brain revealed moderately enlarged ventricles, old right-subcortical lacunar infarcts, and periventricular white-matter disease. He was observed for one more day and discharged to home without incident.
Normal-pressure hydrocephalus (NPH) is a reversible cause of dementia, characterized by enlarged cerebral ventricles with normal intracerebral pressure and the clinical triad of gait disturbance, urinary incontinence, and cognitive dysfunction.1 Its estimated prevalence is 21.9 per 100,000, with higher rates in elderly persons.2 The pathophysiology of the clinical symptoms of NPH is not well understood, but systemic hypertension, poor cerebral venous compliance, and altered levels of inflammatory cytokines may contribute to impaired CSF flow and absorption.3 Treatment involves placement of a ventricular shunt to relieve congestion of cerebrospinal fluid (CSF). Neuroimaging studies have documented reduced cerebral perfusion and vascular reactivity in brain areas adjacent to the ventricles, with improvement after successful shunting.4,5 NPH is a challenging disorder to diagnose and treat, given the high rates of comorbid conditions that share clinical and diagnostic features with it, such as Alzheimer's disease and vascular dementia. Current consensus guidelines regarding diagnosis of NPH as well as common confounding conditions are well described elsewhere.6
Neuropsychiatric Symptoms of NPH
The “frontal–subcortical” dementia pattern of NPH affects processing speed, attention, working memory, and executive function, but spares “cortical” capacities such as praxis, speech, sense modalities, recognition, and long-term memory.7 Noncognitive symptoms are common: 73% of patients in a Japanese study reported significant apathy, and 10% to 25% of patients also reported positive symptoms of delusions, irritability, disinhibition, agitation, anxiety, and stereotyped behaviors.8 NPH patients may also exhibit depression, mania, psychosis, catatonia, obsessive-compulsive behavior, and personality change.8–11 In most case reports, shunting resulted in reduction or remission of the neuropsychiatric symptoms.
Our patient was diagnosed with probable NPH and displayed neuropsychiatric symptoms of abulia, verbal stereotypy, and executive dysfunction. Abulia, a more severe version of apathy, is characterized by lack of spontaneity, deficiency in initiation, inertia, reduction in excursion of motion, poor attention, and easy distractibility.12 Other possible etiologies of the patient’s abnormal mental status, such as seizure, delirium, depression, serotonin toxicity, alcohol withdrawal, and mania were essentially ruled out by the described work-up. Both the old right basal ganglia lacunar infarct, as well as selective serotonin reuptake inhibitor (SSRI) and methylphenidate withdrawal, may have predisposed the patient to development of an abulic state, given reports in the medical literature of apathy ameliorated by methylphenidate.13 It is tempting to speculate that the patient may have displayed signs of NPH much earlier if not for the stimulant in his medication regimen.
Post-Tap Agitation in NPH
After one dose of intravenous midazolam and a large-volume LP, the patient’s apathetic state lysed and quickly evolved into an excited, agitated state that did not respond to intravenous haloperidol. It is unlikely that midazolam caused conversion to prolonged agitation, given the ultra-short half-life of the drug and the subsequent effectiveness of lorazepam. Lumbar punctures may cause headache and carry a small risk of exacerbating tonsillar herniation, but are not normally associated with severe mental status changes in the medical literature. The MRI obtained the day after LP did not show evidence of over-drainage or slit-ventricle syndrome. The only literature describing a similar post-tap agitation is C. Miller Fisher’s 1983 address on abulic and agitated states, where he described five of his own cases of normal-pressure hydrocephalus in which ventriculovenous shunt was followed by a prolonged violent, confused state.14 Fisher’s general theory of agitation postulated a “release” of frontal lobe activity in what he called the “mesencephalic frontal activating system.” By contrast, abulia and akinetic mutism reflected a reduction in this system’s activity. This is supported by the research evidence of increased frontal cerebral perfusion after shunting.4,5
Catatonia is a syndrome of abnormal behaviors and movements due to neuromedical insults that can present in either retarded or excited forms, sharing several clinical features in common with NPH and apathy.15 Severe gait immobility, slowed processing, and incontinence in NPH may be indistinguishable from the stupor, posturing, and negativism of catatonia. Several cases of obstructive hydrocephalus associated with catatonia have been reported, but only one case involving normal-pressure communicating hydrocephalus was reported by Foltz and Ward in 1955.11 The patient in our case may have manifested a syndrome of catatonic stupor with NPH, which transformed into excited catatonia that responded to intravenous lorazepam, which is the first-line treatment for catatonia.
Catatonia in NPH may be underreported for several reasons: the biomechanical etiology of NPH suggests a mechanical treatment, the removal of CSF, rather than medicinal or electroconvulsive therapies as for catatonia; and practitioners in neurological or neurosurgical settings may not be familiar with the syndrome of catatonia. Abulic and catatonic states in NPH should be considered early, as a benzodiazepine challenge can be a safe, rapid, and effective intervention. Dopaminergic agents are occasionally successful in reversing both akinetic mute and catatonic withdrawal cases, which may both be considered mesencephalic frontal activating-system deficit states.