Motor neuropathy due to docetaxel and paclitaxel.

Paclitaxel and docetaxel are novel chemotherapeutic agents that promote the polymerization and inhibit the depolymerization of microtubules. Sensory neuropathy is common with these agents, particularly paclitaxel. We evaluated 64 patients treated with these drugs; 54 were followed prospectively. Eleven (17%, including six of the 54 prospectively followed patients) developed muscle weakness that was predominantly proximal. The weakness was idiosyncratic, occurring at any stage of treatment, had a variable course, and was reversible upon cessation of drug. All patients developed symptoms or signs of taxane-induced sensory neuropathy. Weakness was likely neuropathic in origin; electrodiagnostic studies suggested a distal axonopathy in some patients and proximal denervation (anterior horn cell or nerve root) in other.

Hearing loss in children with brain tumors treated with cisplatin and carboplatin-based high-dose chemotherapy with autologous bone marrow rescue.

Carboplatin is less ototoxic than cisplatin, but ototoxicity may occur with carboplatin at higher doses. We evaluated hearing in children with brain tumors treated with conventional dose cisplatin followed by high-dose carboplatin. Children under 6 years of age, newly diagnosed with brain tumors, were treated after surgery with cisplatin, Etoposide, cyclophosphamide, and vincristine, followed by consolidation with carboplatin, ThioTEPA, Etoposide, and autologous bone marrow rescue. Hearing was assessed before and after consolidation, utilizing standard audiometric techniques. Seven of the 11 evaluable patients developed high-frequency sensorineural hearing loss after induction therapy. Hearing deteriorated after consolidation in five patients, with pure tone threshold shifts of up to 65 dB between 2,000 and 8,000 Hz. Of these five patients, audiological abnormalities were documented in four prior to consolidation, one received cranial irradiation after consolidation, and all five received aminoglycoside antibiotics for at least 2 weeks, with toxic drug levels in four. Three patients have subsequently required hearing aids. Significant ototoxicity is common in these patients. Ototoxicity related to consolidation therapy is likely due to the high dose of carboplatin used, prior cisplatin therapy, aminoglycosides, and, in one patient, cranial irradiation. Audiological assessment is essential in children treated with dose-intensive chemotherapy regimens containing cisplatin and carboplatin for identification and rehabilitation of ototoxicity.

Chemotherapy without radiation therapy as initial treatment for primary CNS lymphoma in older patients.

Chemotherapy plus radiation therapy (RT) for primary CNS lymphoma (PCNSL) has significantly improved patient survival over RT alone, but there are late neurologic sequelae of RT, particularly in the elderly. We treated 13 patients over age 50 years (mean age 74 years) with chemotherapy alone as initial treatment for PCNSL. All received methotrexate (MTX) and procarbazine; in addition, five received thiotepa, four vincristine, and four vincristine and cytarabine. Ten achieved a complete response (CR), 2 a partial response (PR), and 1 progressed through treatment. Two patients with ocular lymphoma responded to MTX, procarbazine, and vincristine. Four of six patients who relapsed after achieving a CR or PR were treated with additional chemotherapy or RT; three achieved a CR and one a PR. Five patients remain in CR at 7.5 to 30 months, one is alive at 35 months but with progressive disease, six died of PCNSL at 5 to 30.5 months, and one died in CR of sulfur allergy 2 months after diagnosis. The Karnofsky Performance Status improved in 11 to 13 patients with treatment. Cognitive deficits were present in nine patients at diagnosis and improved in eight of these nine after chemotherapy. Only one patient developed new cognitive deficits, due to progressive tumor and possibly MTX leukoencephalopathy. Chemotherapy alone for PCNSL is effective in the elderly and eliminates the risk of RT-related neurotoxicity. RT can salvage those who relapse after chemotherapy.

Primary central nervous system lymphoma.

The rising incidence of PCNSL has allowed a greater understanding of the clinical features and behavior of this once rare tumor. Factors such as dissemination of tumor within the central nervous system, the presence of tumor behind an intact blood-brain barrier, as well as leptomeningeal and ocular involvement must be considered in the design of treatment protocols for this disease. The addition of chemotherapy has made a significant impact on the treatment of PCNSL, but the prognosis of PCNSL remains worse than for comparable systemic non-Hodgkin's lymphomas. With continued development of chemotherapy regimens, the hope is for improved survival without the need for potentially neurotoxic radiation therapy.

Isometric strength and thickness relationships in human quadriceps muscle.

The isometric Maximum Voluntary Contraction (MVC) of the right quadriceps femoris muscle was measured in 82 females and 58 males using a chair dynamometer and their mid-thigh quadriceps thickness was measured using real-time B-mode ultrasound. Statistically significant relationships (ranging from P < 0.001 to P < 0.0001) were found between quadriceps MVC, quadriceps thickness and body weight for both males and females. A significant inter-sex difference was present in the MVC-weight and MVC-thickness relationships, with males tending to have a higher MVC for a given body weight (P < 0.0001) and for a given muscle thickness (P < 0.0001). The inter-sex difference in the force-size relationship may relate to the previously demonstrated larger size of type 2b fibres and to the greater force generating capacity of these fibres compared with type 1 fibres.

Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis.

The diagnosis of leptomeningeal metastasis is often difficult and usually requires the demonstration of malignant cells in the cerebrospinal fluid. Neuroimaging, however, may establish or support the diagnosis in some patients. Radiographic abnormalities consistent with or suggestive of leptomeningeal metastasis include leptomeningeal, subependymal, dural, or cranial nerve enhancement; superficial cerebral lesions; and communicating hydrocephalus. We evaluated 137 cancer patients with clinical symptoms suspicious for leptomeningeal metastasis with neuroimaging or cerebrospinal fluid cytology or both. Neuroimaging findings were abnormal in 70 of 128 tested patients; cytology was performed in 58 of these 70 and the results were positive in 37. Conversely, cytological findings were positive in 53 of 115 tested patients; neuroimaging was performed in 49 of these 53 and the findings were abnormal in 37 (26/29 solid tumors and 11/20 hematological tumors). Of the total series of 137 patients, leptomeningeal metastasis was diagnosed in 77; in 24 (31%) the diagnosis was made on the basis of clinical picture and abnormal neuroimaging alone. Neuroimaging is a valuable tool in the investigation of leptomeningeal metastasis in the cancer population, and the presence of typical clinical features together with appropriate neuroimaging abnormalities is adequate to make the diagnosis of leptomeningeal metastasis even if cerebrospinal fluid cytological results are negative.

Central nervous system progression of metastatic breast cancer in patients treated with paclitaxel.

BACKGROUND: The possibility of tumor sanctuary sites in the central nervous system (CNS) of patients receiving paclitaxel has been suggested by laboratory data identifying low concentrations of drug in the brain and cerebrospinal fluid (CSF) of rats. METHODS: The pattern of disease progression in patients with metastatic breast cancer who had an initial response to paclitaxel treatment in five Phase II trials at the Memorial Sloan-Kettering Cancer Center was reviewed. RESULTS: Of 152 patients, 53 had a partial or complete response, and 25 had a minor response. Of the 78 patients who responded to paclitaxel, 52 had subsequent disease progression, 22 changed treatments before progression occurred (as specified by the protocol and/or to receive high dose consolidation chemotherapy), 2 stopped receiving treatment because of toxicity, 1 continued receiving treatment, and 1 died with no evidence of disease progression. Six of the 52 patients who progressed after initially responding to paclitaxel had isolated CNS progression while maintaining their systemic response (leptomeningeal metastasis in three, brain metastases in two, brain and leptomeningeal metastases in one). One patient had CNS progression (brain metastases) associated with other systemic sites of progression. All patients with CNS disease developed neurologic symptoms, prompting neurologic evaluation; one had only a mild headache, which was not recognized until evaluation for paclitaxel-related peripheral neuropathy. CONCLUSIONS: These data suggest that the CNS, and particularly the CSF, is an important sanctuary site for patients with metastatic breast cancer receiving paclitaxel.

Adenocarcinomatous transformation of intracranial germ cell tumors.

Germ cell tumors arising in the gonads, retroperitoneum, and mediastinum are occasionally overgrown by cancers of somatic type that are widely assumed to derive from the "malignant transformation" of included teratomatous tissues. These malignant, nongerminal neoplasms are typically chemoresistant, and their emergence is often associated with fatal treatment failure. Only rare, well-documented reports of sarcomatous transformation complicating intracranial germ cell neoplasia are on record. We describe two nongerminomatous germ cell tumors of the pineal region that underwent transformation into enteric-type adenocarcinoma. Both recurred in a locally aggressive fashion, one proving rapidly fatal owing to the development of multiple cerebral and cerebellar metastases and spinal leptomeningeal adenocarcinomatosis.

Alcohol and drug abuse.

Neurological complications are well recognized with alcohol abuse, and an increasing amount of literature is emerging describing neurological disease as a complication of other drugs of addiction (recreational drugs). This review covers recent papers related to alcohol and drug abuse.

Choreoathetosis and thalamic haemorrhage.

A case of choreoathetosis due to thalamic haemorrhage and responding to pimozide is described. The anatomical changes, the neurotransmitter abnormalities and the drug treatment of chorea are discussed.