A 70 year old man comes to clinical attention with progressive memory loss, urinary incontinence, and gait instability. MRI of the brain shows dilatation of the ventricular cavities, while the cerebral coex appears normal. No infarcts are seen. Repeated lumbar punctures reveal occasional increases in cerebrospinal fluid (CSF) pressure. A biopsy of the frontal coex demonstrates the absence of neurofibrillary tangles and senile plaques. Which of the following is the most appropriate treatment?
This is an "interdisciplinary" question, which begins with a clinical scenario and ends by testing your knowledge of pathophysiology and pharmacology. The clinical presentation has the classic triad of memory loss, urinary incontinence, and gait abnormalities characteristic of normal pressure hydrocephalus (recently renamed intermittently raised pressure hydrocephalus). This condition results from intermittent increases in CSF pressure, leading to progressive damage to cerebral white matter and dilatation of the ventricles. No significant coical atrophy is present. The lack of Alzheimer-related changes in the biopsy and the measurements of CSF pressure suppo the diagnosis. Relief of CSF pressure can be obtained by placing a ventricular shunt, which usually improves clinical symptomatology. Tacrine and other inhibitors of acetylcholinesterase are used in the symptomatic therapy of Alzheimer disease. The pathology of this disease includes degeneration of cerebral cholinergic systems, such as the basal nucleus of Meyne, which project to the neocoex and are involved in memory and learning. Acetylcholinesterase degrades acetylcholine after release from presynaptic boutons. Acetylcholinesterase inhibitors therefore enhance the concentration of acetylcholine and amplify cholinergic neurotransmission. Aspirin is used to prevent aggregation and adhesion of platelets in patients with risk factors for cerebrovascular disease. Prophylactic aspirin treatment lowers the incidence of transient ischemic attacks and brain infarcts. L-DOPA is a precursor of dopamine, the neurotransmitter of the nigrostriatal neurons that degenerate in Parkinson disease. L-DOPA, especially in combination with a peripheral decarboxylase inhibitor, is therefore used in the treatment of this disorder. Ref: Ropper A.E., Ropper A.H. (2012). Chapter 209. Intracranial Hemorrhage and Related Conditions. In G.V. Lawry, J. Matloff, D.D. Dressler, D.J. Brotman, J.S. Ginsberg (Eds), Principles and Practice of Hospital Medicine.
Acetylcholinesterase inhibitors such as tacrine
Aspirin
L-DOPA
Ventricular shunt