Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice.

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals - regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended.

A Rare Case of Docetaxel-Induced Hydrocephalus Presenting with Gait Disturbances Mimicking and Coexisting with Taxane-Associated Polyneuropathy: The Relevance of Differential Diagnosis, Clinical Assessment, and Response to Ventriculoperitoneal Shunt.

Docetaxel constitutes a widely used chemotherapeutic agent as a first-line treatment for several neoplastic diseases. One of the most common side effects induced by this drug is polyneuropathy, which among other symptoms can cause gait disbalance. However, in exceptional cases gait disturbances could be related to docetaxel-induced hydrocephalus, a rare event that up to the present has been overseen throughout the medical literature and should be meticulously differentiated from polyneuropathy, since its clinical features, treatment, and prognosis differ drastically. We present the case of a woman with a progressive gait disturbance that started immediately after having been treated with docetaxel for breast cancer resembling the same clinical characteristics as seen in patients affected by normal pressure hydrocephalus. The symptoms had been observed for about 2 years as having been caused only by polyneuropathy, given the high incidence of this side effect and the accompanying numbness of distal extremities. However, brain MRI evidenced a marked enlargement of the ventricular system. Brain metastases as well as carcinomatous meningitis were ruled out. After having placed a ventriculoperitoneal shunt, the patient showed a rapid, long-lasting and outstanding improvement of gait performance. We discuss the coexistence, in this case, of taxane-associated hydrocephalus and polyneuropathy and describe the clinical features, assessment and surgical outcome of docetaxel-induced hydrocephalus, since its early recognition and differentiation from the highly frequent taxane-associated polyneuropathy has relevant consequences for the management and treatment of these patients.