Natalizumab and drug holiday in clinical practice: an observational study in very active relapsing remitting multiple sclerosis patients.

BACKGROUND: In order to reduce the risk of progressive multifocal leucoencephalopathy when using natalizumab for more than 12 months, a 6-month drug holiday has been discussed. However, the consequences on short term disease activity have been poorly assessed. OBJECTIVE: The aim of this study was to assess clinical and radiological disease activity within 6 months after stopping natalizumab in very active relapsing remitting Multiple Sclerosis (RRMS) patients. METHODS: In 8 hospitals from Western France, we retrospectively collected clinical and MRI data from consecutive RRMS patients treated with natalizumab for at least 6 months, and who stopped the drug for various reasons except therapeutic failure. Patients didn't receive any other disease modifying treatment after discontinuing natalizumab. RESULTS: A total of 27 patients with very active RRMS before natalizumab start (mean annualized relapse rate of 2.3, MRI activity in 21 of 27 patients) were studied. Within 6 months after discontinuing natalizumab, 18 patients (67%) experienced clinical relapse and 3 additional patients had radiological activity, without clinical relapse. Four patients (15%) experienced a rebound activity, with severe relapse and 20 or more gadolinium enhancing lesions on MRI. CONCLUSION: Such observational data didn't support the concept of drug holiday when using natalizumab in very active RRMS.

[Multiple cerebral infarcts associated with livedo secondary to anti-cancer therapy with interleukin 2 and interferon alpha]. / Infarctus cérébraux multiples associés à un livedo secondaires à un traitement anticancéreux par interleukine 2 et interféron alpha.

Anticancer drugs rarely cause strokes. We report the case of a woman treated for a kidney cancer by IL2 and IFN alpha, having developed multiple strokes associated with a livedo. The responsibility of IL2 and IFN alpha seemed likely. The association with a transitory livedo suggested that the pathological process might be a cerebral angiopathy with arterial vasospasms.

[Amnesic syndrome caused by limited infarction in the right anterior thalamus]. / Syndrome amnésique par infarctus restreint du thalamus antérieur droit.

A case of global and persistent amnesia due to a right polar and anterior thalamic infarction is reported. There was a moderate impairment of attention and categorization ability. The amnesia was primarily anterograde, with partial disturbance of short-term memory and severe deficit of long-term memory for verbal and visuo-spatial materials. A severe increase of pro-active interference was present. Retrograde memory was mildly affected. Two years later, a second infarction in the right thalamo-sub-thalamic territory occurred, increasing the deficits of attention, short-term memory and recall.

[Secondary and late development of hematoma of the brain stem]. / Evolution secondaire et tardive des hématomes du tronc cérébral.

The functional and social outcome in 15 patients with brainstem hematomas surviving on the 15th day is reported. At the end of the first year post stroke, the main neurological deficits were sensory, postural and paresis of the 6th and 7th cranial nerves. This resulted from the preferential location of the lesions in the lateral and posterior pons. On a functional point of view, 8 patients were independent in daily living. Seven of them were regularly engaged in more elaborated activities, at home and outside: 1 had recovered his previous professional activities. Those functions evolved more slowly during the 2nd year and later on. A significant correlation was found between the initial neurological status and the functional outcome at 1 year, and also between the volume of the hematoma on C.T. scan and this outcome. In this series, the age of the patients was not correlated to the other variables.

[Cerebral blood flow deficit and thalamic infarcts. Topographic and neuropsychological confrontations]. / Débit sanguin cérébral et infarctus thalamiques. Confrontations topographiques et neuropsychologiques.

Cerebral blood flow (C.B.F.) measurements with continuous xenon 133 inhalation and single photon emission tomography were performed in 11 patients with uni- or bilateral thalamic infarctions. Anterior infarction was associated with changes in parietal and anterior frontal C.B.F., thalamo-subthalamic infarctions with a more diffuse and definite reduction of C.B.F., thalamo-geniculate and superior juxta-thalamic lesions to a reduction of temporal and parietal C.B.F. A relative anatomo-functional concordance was found between the localization of the infarction and the cortical and deep situation of the C.B.F. reduction. Relations between the site of this reduction and the quality and degree of neuropsychological involvement were less clear. A verbal activation was realized in a patient with thalamo-subthalamic infarction which failed to evoke the C.B.F. elevation observed in normal subjects.

[Tomographical use of Tc hexamethylpropylene amine-oxime. First experience (78 studies)]. / Utilisation tomographique de l'hexaméthylpropylène amine-oxyme Tc. Première expérience (78 études).

A new radiotracer of cerebral perfusion, 99mTc-labelled hexamethylpropylene amine-oxime, has been tried in 78 subjects: 6 controls and 72 patients. Qualitatively, the distribution of this tracer in healthy subjects was very much the same as that obtained with a reference method using 133xenon inhalation. Quantitatively, there was no correlation between the real blood flow rate and the normalized cerebral uptake rate. On the other hand, the asymmetry indices obtained in controls (but also in 16 patients) correlated very closely with those obtained with 133xenon. Our first results in acute ischaemic diseases as well as in the evaluation of vasospasm or Alzheimer-like presenile dementia point to wide fields of application for the new compound. Unlike its predecessors, it is always available and will probably be used, without any logistic investment, with the standard equipment of all Nuclear medicine departments.

Operative treatment of thoraco-lumbar metastases, using methylmetacrylate and Kempf's rods for vertebral replacement and stabilization. Report of 15 cases.

The authors report their experience in the treatment of 15 cases in thoracolumbar metastases with spinal cord compression. A decompressive laminectomy was routinely performed and followed by a transversoarthropediculectomy. Most part of the neoplastic tissue was removed from the epidural space, vertebral body and retroperitoneal or retro-pleural areas. Complete decompression of the nervous elements was always achieved. Stabilization was obtained by replacement of the neoplastic vertebral body with a methylmetacrylate prothesis and eventually by Kempf's compression instrumentation. The surgical treatment was completed in a single stage operation, by a classical posterolateral approach. Orthopaedic, neurologic and oncologic advantages of this treatment are discussed.

[Regional cerebral blood flow and its reactivity to acetazolamide in transient ischemic attacks. Study of 20 cases by gamma emission tomography]. / Le débit sanguin cérebral local et sa réactivité à l'acétazolamide dans les accidents ischémiques transitoires. Etude de 20 cas par tomographie d'émission gamma.

We have studied regional cerebral blood flow (= test) and reactivity of acetazolamide injection (= retest) in 20 patients who had presented transient ischemic attacks (TIA). The cerebral blood flow was measured by the atraumatic Xenon 133 inhalation method and single photon emission tomography using a specially dedicated tomograph (TOMOMATIC 64), allowing 3 tomographic levels (OM + 1, + 5, + 9 cm). Measurements were realized in a quiet, dark room. Acetazolamide (500 mg or 1000 mg) was injected intravenously immediately after the test, and the retest was performed 15 minutes after, in the same conditions. Results obtained from paired ROIS were analysed in terms of asymmetric index for the test, of relative reactivity for retest in regard of normal values established in a group of healthy volunteers. All patients had neurological examination, vascular explorations and CT scan. Six of the patients showed a bad reactivity (abolished or strongly decreased) which was evoked a significant hemodynamically stenosis, reflecting the loss of collateral capacity. In the other group results were diversified, and we classified these in 4 groups: "normal" (7), "luxury perfusion" (3), "limited infarction" (1), and "incomplete infarction" (3). When these groups were plotted versus duration of onset and delay between the last attack and the moment of the measurement, "incomplete infarction" clearly appears as a step between brief TIA (less of 1 hour) and "limited infarction". So rCBF and reactivity to acetazolamide are of major interest for the physiopathological classification of TIAs, but also for treatment and prognosis.

[Indications for surgical treatment in dorsal disk pathology. 34 cases]. / Indications du traitement chirurgical en pathologie discale dorsale. Trente-quatre observations.

Thirty-four patients were operated for dorsal disk pathology by a postero-lateral approach. The first cases have been followed-up for over 4 years and have shown this method to be reliable. When associated with the "harpoon" marker technique, the surgical indications now include not only patients with progressive radiculo-medullary symptoms, but also cases of sudden decompensation and those limited to radicular symptoms.

[Medullary compression due to vertebral angioma in pregnancy. A case treated by embolization]. / Compression médullaire par angiome vertébral au cours de la grossesse. Un cas traité par embolisation.

A previously healthy 24 year old woman presented a progressive paraplegia during the third trimester of her second pregnancy. Partial improvement occurred after caesarian. The neuroradiological study revealed spinal cord compression by an extensive corporeo-pedicular angioma of the T2 vertebrae. Almost total recovery occurred after selective embolization. The occurrence of neurological complications of vertebral angiomas during pregnancy is rarely reported in the literature. Mechanisms of the spinal cord compression and their relations with the pregnancy are discussed and difficulties for diagnosis and treatment are emphasized. When technically possible, the embolization appears to be the most adapted treatment, especially for these extensive types of vertebral angioma.