A double-blind, placebo-controlled, enriched population study of tacrine in patients with Alzheimer's disease.

The efficacy of tacrine in the treatment of patients with probable Alzheimer's disease (AD) was evaluated in a double-blind, placebo-controlled, enriched population multicenter study in France. A total of 280 patients entered the dose titration phase of the study. The assessment of potential benefit of tacrine ("best dose") was based on demonstrating improvement on the Alzheimer's Disease Assessment Scale (ADAS) total score versus a blinded placebo. One hundred and thirty of 242 (54%) patients achieved a "best dose" and were eligible for the double-blind, parallel group (pivotal) phase. Primary efficacy measures were ADAS-Cognitive and Clinical Global Impression of Change; secondary efficacy measures of cognition and activities of daily living were also included. Results indicated that tacrine-treated patients showed improved functioning based on the ADAS-Cognitive in comparison to placebo-treated patients. Transaminase elevations above the upper limit of normal occurred in 32% of patients, were more frequent in women than in men, demonstrated a delayed onset, and returned to normal limits for all patients following discontinuation of treatment The results from this study are supportive of the efficacy of tacrine in the treatment of AD as demonstrated in a study of similar design conducted in the US and studies using different designs.

[Clinical amyotrophic lateral sclerosis syndromes in gammapathies: clinical, electrophysiologic and histoimmunologic aspects]. / Syndromes cliniques de SLA au cours des gammapathies: aspects cliniques, électrophysiologiques et histoimmunologiques.

Eleven patients with motor neuron disease associated with a monoclonal gammopathy were studied. One patient had a previously known multiple myeloma. In the other patients neurological symptoms preceded diagnosis of the gammopathy by one month to 8 years. They were 5 multiple myeloma, 1 macroglobulinemia, 1 chronic lymphatic leukemia, 1 lymphoma and 3 benign monoclonal gammopathies. EMG and motor conduction velocities results were consistent with anterior horn cell disease but sensory conduction studies were abnormal in seven cases out of eight. Superficial peroneal nerve biopsy performed in all patients confirmed peripheral nerve involvement. The relations between gammopathy, clinical symptoms and electrophysiological data are discussed. The interest of sensory conduction studies in every patient with motor neuron disease is emphasized.

[Deafness and tinnitus in flare-ups in 10 cases of multiple sclerosis]. / Surdité et acouphènes lors de poussées dans 10 cas de sclérose en plaques.

Deafness in multiple sclerosis is rare, being reported in less than 1 p. 100 of the cases. Ten cases of deafness associated with tinnitus during acute episodes of multiple sclerosis are presented, the diagnosis being definite in 9 patients and probable, according to McAlpine's criteria, in the tenth case. These were not cases where routine examinations demonstrated a latent hearing defect, but were all patients with sudden, often unilateral, incapacitating deafness during an acute episode of the disease, with regression usually after less than 3 months. Deafness recurred in 3 patients and was the initial symptom in 5 cases. Serial audiometric examinations were performed in most cases together with recordings of various evoked potentials, including early auditory evoked potentials during or after the onset of deafness in all 10 patients. BAEPs abnormalities were noted in 8 and appeared to be correlated more with brain stem demyelinization, as it has been established for a few years, than with the deafness itself. Severe anomalies of auditory evoked potentials regressed after the acute episode in only 1 patient. Lesions of the auditory pathways within the brain stem appear to be the cause of the deafness, as shown by results of auditory tests, which pointed to a central origin. The onset of deafness did not indicate a particular progression of multiple sclerosis.

[Non-syringomelic medullary syndrome with Arnold-Chiari malformation (author's transl)]. / Syndromes médullaires non syringomyéliques et difformité de Chiari.

The authors present 15 observations of a medullary syndrome of the non-syringomelic type, in patients with Arnold-Chiari's malformation (type I; 13 times - type II; twice), verified surgically, and without severe malformations of the occipito-vertebral articulation. Brown-Sequard's disease was present in 6 cases, subacute combined degeneration in 2 cases, and pyramidal lesions were very predominant in two other cases. The last 5 cases had cordonal signs associated with signs of disturbance of the anterior horns in the medulla, affecting all four limbs, and more especially the lower limbs. In four cases the medullary cavity was exposed, and in two cases extended along the whole length of the cord up to the terminal cone. The literature is reviewed and diagnostic and pathogenic problems raised by these myelopathies are discussed. They merit systematic investigation.

[Study of neurological manifestations of chronic lymphatic leukemia (lymphosis). Role of associated globulin anomalies (apropos of 8 cases)]. / Contribution à l'étude des manifestations neurologiques des leucémies lymphoïdes chroniques (lymphoses). Role des anomalies globuliniques associées (a propos de huit observations)

The authors emphasize the relative frequency of neurological symptoms in lymphatic leukaemia. Clinically, these cause more or less diffuse encephalitic or multineuritic syndromes, generally a combination of the two. Their pathogenesis is usually connected with lymphoid tissue infiltration into either the meninges or the vascular sheaths of the central nervous system or the sheaths of the roots or of the peripheral nerves. The authors stress the possible function of immunoglobulin abnormalities of the C.S.F. indicative of the presence of the leukaemic process within the nervous system. This pathogenesis prompts the use of therapeutic methods directly attacking leukaemic infiltration of the nervous system (focal cobalt therapy, intrathecal chemotherapy) and the authors have found that these give favourable results.