Donepezil in the treatment of opioid-induced sedation: report of six cases.

Donepezil, an oral acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, was given to 6 cancer pain patients having sedation related to the analgesic use of opioids. Each patient was taking more than 200 mg of oral morphine equivalents per day, and several were receiving complex analgesic regimens consisting of multiple adjuvant medications. Sedation improved at least moderately in 5 of the patients and mildly in 1 after they began taking donepezil. Patients reported a decrease in episodes of spontaneous sleeping during the day, fewer myoclonic twitches, improved daily function and greater social interaction. Several also reported improved sleep at night. Analgesia was not compromised by the use of donepezil, and in some cases it appeared improved. Donepezil may be a valuable alternative to psychostimulants in the treatment of opioid-induced sedation. A prospective controlled trial comparing the treatment effects of psychostimulants and donepezil on patients having opioid-induced sedation is underway.

Eye movement disorders in bone marrow transplant patients on cyclosporin and ganciclovir.

After 582 allogeneic bone marrow transplants, we have encountered four patients (0.7%) who developed transient unilateral or bilateral sixth nerve palsies. Three of the four patients also had bilateral ptosis. These signs resolved 24-48 h after cyclosporin and ganciclovir were discontinued. One patient had MRI T2 abnormalities compatible with cyclosporin neurotoxicity. We postulate that cyclosporin, possibly together with ganciclovir, can produce transient brain stem or neuromuscular dysfunction with eye movement abnormality in occasional patients.

Acute polyneuropathy after high dose cytosine arabinoside in patients with leukemia.

BACKGROUND: Peripheral nerve toxicity has been reported but is not a commonly recognized complication of high dose cytosine arabinoside (HDAC) therapy. This study was undertaken to estimate the prevalence and describe the clinical spectrum of acute polyneuropathy associated with HDAC therapy for leukemia. METHODS: Records of 153 acute leukemia patients who received 194 courses of HDAC at the City of Hope were reviewed for evidence of severe peripheral neuropathy with onset 2-3 weeks after HDAC therapy. RESULTS: Two patients were identified who developed motor disability 2-3 weeks after HDAC therapy, and the disability progressed in a monophasic course to quadriparesis. There was neurophysiologic evidence of peripheral nerve demyelination with slowed nerve conduction velocities and conduction block. One patient who was autopsied had demyelination identified in luxol-fast blue sections of peripheral nerve (with Bielschowsky-stained sections showing intact peripheral nerve axons). There were foamy macrophages in the peripheral nerve but no chronic inflammatory cells. For comparison, data from these two patients were combined with those from four published case reports of polyneuropathy associated with HDAC therapy. Quadriparesis occurred in five of six cases with the need for ventilatory support in four. Cerebrospinal fluid protein was elevated in five of six cases. Etiologic evidence incriminating HDAC included simultaneous cerebellar signs in two of six cases and a narrow interval of clinical onset after HDAC therapy. CONCLUSIONS: Demyelinating polyneuropathy occurs in approximately 1% of HDAC courses and produces severe motor disability. HDAC immunosuppression could trigger an immune-mediated neuropathy; alternatively, a direct neurotoxic effect of HDAC on Schwann cells is also an etiologic possibility.

Immune-mediated myelopathy after allogeneic marrow transplantation.

We describe two patients who developed myelopathy 15 and 27 months after allogeneic marrow transplantation. Exacerbations of the myelopathy occurred, with the development of optic neuropathy in one patient when corticosteroid therapy was tapered. The other patient had two exacerbations, 28 months and 40 months after transplantation, both of which resolved with plasma-pheresis. These case reports suggest that immune-mediated disease after transplantation can affect the central nervous system.

Exacerbation of inflammatory demyelinating polyneuropathy after bone marrow transplantation.

Two patients with hematologic malignancy and quiescent inflammatory demyelinating polyneuropathy developed severe exacerbations of polyneuropathy at the time of bone marrow transplantation. The clinical course in both patients was progressive despite therapy with immuno-suppressive agents, plasmapheresis, and high dose immunoglobulin. The polyneuropathy resulted in quadriplegia which contributed to the patients' deaths 175 and 48 days after transplantation. Sections of multiple peripheral nerves sampled post mortem in the first case revealed prominent demyelination with heavy infiltration of macrophages and lymphocytes. Immunohistochemical studies demonstrated that most of the lymphocytes were of the CD8+, cytotoxic/suppressor cell class and that many of the Schwann cells expressed class II (HLA-DR) antigen. This report suggests that bone marrow transplantation can exacerbate inflammatory demyelinating polyneuropathy.

Papilledema in the metastatic jugular foramen syndrome.

In a patient with Ewing's tumor, bilateral papilledema developed along with a left jugular foramen syndrome. Plain tomograms demonstrated a metastasis at the base of the skull. A digital intravenous angiogram showed an occlusion of the left transverse sinus at the level of the jugular foramen. The papilledema was explained by an increase in the intracranial pressure due to the rapid obstruction of venous drainage by the metastasis.