No increase in cancer incidence detected after cyclophosphamide in a French cohort of patients with progressive multiple sclerosis.

BACKGROUND: Cyclophosphamide is still used in progressive forms of multiple sclerosis (MS) in view of its suggested efficacy and safety in the short term. No data exist on its long-term safety in MS, particularly on the risk of malignancy. OBJECTIVE: The objective of this study was to evaluate cancer incidence in MS after cyclophosphamide treatment. METHODS: We performed a historical prospective study in a cohort of MS patients treated with cyclophosphamide. We collected demographic data and medical history from medical databases and patient interviews. Reported cancers were histologically confirmed. Cancer incidence was compared with the incidence in the general population by estimating standardized incidence ratios (SIRs). RESULTS: We included 354 patients, with a median follow-up of 5 years (range 2-15) after cyclophosphamide treatment. Fifteen patients developed a solid cancer, which occurred at a median of 3 years (range 0.5-14) after cyclophosphamide introduction. The cumulative incidence of cancer after cyclophosphamide was 3.1% at 5 years and 5.9% at 8 years. We found no increase in cancer incidence after cyclophosphamide treatment in men (SIR = 0.83, 95% confidence interval [CI] 0.30-1.82), women (SIR = 0.99, 95% CI 0.43-1.95), or men and women combined (SIR = 0.92, 95% CI 0.50-1.54). CONCLUSION: We found no evidence of an increased risk of cancer associated with cyclophosphamide treatment in MS patients.

Regressive dystonia and cerebellar ataxia: two unusual symptoms in central pontine myelinolysis.

Two patients with central pontine myelinolysis who presented with dystonia are described. In one, it was associated with cerebellar ataxia which spontaneously improved. In the second, dystonia progressively disappeared 6 months later. In both cases magnetic resonance imaging (MRI) revealed characteristic pontine lesions. Extrapontine myelinolysis involving the putamen was also observed in one patient. Even when the basal ganglia seem to be spared on MRI, dystonia is probably due to their involvement by myelinolysis. Cerebellar ataxia may be related to peduncular or cerebellar lesions or both.

Cognitive and psychiatric impairment in herpes simplex virus encephalitis suggest involvement of the amygdalo-frontal pathways.

The long-term neuropsychological and psychiatric sequelae of herpes simplex virus encephalitis (HSVE) and their relationship to the volume of temporal lesions and to amygdala and hippocampus damage remain undefined. We have conducted a prospective study of long-term sequelae in 11 patients with clinically presumed HSVE and detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction. Six months after encephalitis, patients underwent neuropsychological and language assessment. At the same stage, single photon emission computed tomography (SPECT) evaluated the occurrence of hypoperfusion with an index of asymmetry. MRI was used for the measurement of amygdala, hippocampus and cerebral lesions by two blind neurologists. The volume of the amygdala and hippocampus was compared with those of five controls, matched for age and level of education. Long-term memory disorders were seen in 6 patients, associated with the larger lesions and damage of at least two structures. Long-term behavioural changes with emotionalism, irritability, anxiety or depression were prominent in 7. Left prefrontal hypoperfusion appeared in 8 patients, associated with psychiatric disorders in 7 and left amygdala damage in 6. The reduction of amygdala and hippocampus volume was correlated with the overall volume of lesions. Different patterns of mesial temporal lobe damage occurred, involving either amygdala alone, or amygdala and hippocampus, but never hippocampus alone. MRI volumetric measurements in HSVE could be a good indicator of long-term prognosis. Persistant behavioural changes could be related to an amygdala and frontal dysfunction.

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile.

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.

[A case of spongiform encephalopathy mimicking cortico-basal degeneration]. / Encéphalopathie spongiforme mimant une dégénérescence corticobasale.

INTRODUCTION: The presentation of subacute spongiform encephalopathies is varied and includes various movement disorders such as parkinsonism, myoclonus, or dystonia. These signs, especially when asymmetrical, can lead to the diagnostic of corticobasal degeneration. CASE REPORT: We report the case of a 75-Year-old woman who developed clinical signs suggestive of corticobasal degeneration: asymmetric rigidity and apraxia, limb dystonia, and postural instability. The final diagnosis of spongiform encephalopathy was suspected because of rapid decline and confirmed by post-mortem examination. CONCLUSION: This case highlights the importance of considering subacute spongiform encephalopathy in patients with a clinical presentation compatible with corticobasal degeneration.

[Post-radiotherapy stenosis of the supraclinoid internal carotid artery. Moyamoya network]. / Sténose post-radiothérapique de l'artère carotide interne supraclinoïdienne. Réseau de Moyamoya.

A 36 year-old caucasian woman was operated and then irradiated for a pituitary adenoma. Two years later, a left anterior temporal lobectomy for a grade I astrocytoma was performed. Four years later, she experienced right hemiparesis and aphasia. CT scan showed a left temporo-occipital low density area. A left carotid angiogram showed a narrowing of the left carotid artery beginning in the lower part of the siphon and progressing to a complete supraclinoid occlusion. There was a collateral circulation of the Moyamoya type. Radiation-induced narrowing or occlusion of the intracranial internal carotid artery is an infrequent finding. Most cases appear in young subjects, several years after a high dose of radiation therapy (30 to 60 grays). Some cases may show a network of the Moyamoya type. Usually, the absence of vascular abnormalities prior to radiation cannot be demonstrated. In our case, as in 3 other cases of the literature, the intracranial vessels were of normal appearance before irradiation. The vascular lesions can thus be considered as acquired and secondary to radiation therapy.

[Obsessive-compulsive behavior and progressive supranuclear palsy]. / Comportement compulsif d'allure obsessionnelle et paralysie supranucléaire progressive.

A case of progressive supranuclear palsy characterized by a loss of self-activation and a compulsive behaviour of the obsessive type is reported. The pathological examination was remarkable for the intensity of pallidal lesions and their diffusion to both the external and internal segments. While the loss of self-activation seemed to result from a damaged cortico-subcortical circuit forming a limbic loop, the compulsive behaviour of the obsessive type may have resulted from the interruption of a frontal-caudal-pallidal-luysian circuit.

[Internal carotid occlusion and essential thrombocythemia. 2 cases]. / Occlusion carotidienne interne et thrombocythémie essentielle. 2 cas.

We report 2 cases of occlusion of the internal carotid artery in young, non-atherosclerotic patients with essential thrombocythemia (ET). This complication of ET seems to be rare, but is probably underdiagnosed since transient ischemia, which is frequent in ET patients, is seldom explored by angiography. The excess of thrombocytes and the thrombopathy may account for the microvascular complications, but in the absence of any other contributory factor, occlusions of large arteries, such as the ICA, is more difficult to explain.

[Value of gene amplification of herpesviruses in the diagnosis and treatment of acute viral encephalitis]. / Valeur de l'amplification génique du virus herpétique dans le diagnostic et le traitement des encéphalites aiguës virales.

Positive diagnosis of Herpes simplex virus (HSV) encephalitis was rarely obtained in the past, when brain biopsy had been performed. Other tests (HSV antigen and HSV antibodies detection and interferon alpha measurement, in cerebrospinal fluid) failed to prove HSV infection. Polymerase chain reaction has been proposed for accurate and rapid diagnosis of HSV encephalitis. With 35 cycles of a DNA polymerase sequence duplication, sensitivity reaches 95% and specificity 100%. HSV PCR is a useful tool for the diagnosis of acute encephalitis. This should be available in many neurologic clinics. Therapeutic consequences include rapid disruption of aciclovir when clinical features, MRI study and negative PCR suggest non herpetic encephalitis.

[Recurrent coma, papular mucinosis and benign dysglobulinemia]. / Comas répétés, mucinose papuleuse, dysglobulinémie bénigne.

A woman presented with a history of three regressive comas of undetectable etiology between the age of 52 and 57 years. An IgG lambda benign monoclonal dysglobulinemia was combined with a papular mucinosis (myxedematous lichen or the generalized form of Arndt-Gotton's scleromyxedema). In the 6 analogous cases documented in the literature the onset of coma occurred generally several weeks after an aggravation of the cutaneous lesions. The coma was preceded by an influenza-like syndrome followed by asthenia, malaise with vertigo and frequently epileptic seizures. During recovery, hallucinations and transient hepatic disorders were noted. Pruritus with pronounced hypereosinophilia preceded desquamation and regression of dermatologic lesions. These comas can lead to a fatal outcome (2 of 7 cases) or regress in 2 to 20 days usually without sequelae. The disease is probably of immunologic origin. The paraprotein or a serum factor could exert a direct toxic effect on brain. As in neurologic manifestations of malignant dysglobulinemia, explained initially by a "toxic encephalosis, clinical, angiography, biologic and immunologic data exist in favor of blood hyperviscosity. This hyperviscosity could result from polymer formation through intermediates immunoglobulins and other protein chains, or again from alteration of deformability of red cells by binding of paraprotein. Hyperviscosity syndromes are frequent in system diseases that are often associated with papular mucinosis. Whatever the exact mechanism of these "comas due to papular mucinosis", a logical choice is their treatment by immunosuppressants and plasmapheresis: in the case reported, the use of plasmapheresis as soon as premonitory signs had appeared probably prevented a fourth coma.

[Treatment of progressive multiple sclerosis with cyclophosphamide]. / Traitement des formes progressives de sclérose en plaques par le cyclophosphamide.

Intravenous (IV) cyclophosphamide is currently used in secondary progressive (SP) and Primary progressive (PP) Multiple Sclerosis (MS) but its efficacy remains uncertain. Furthermore, it is necessary to determine which MS should be successfully treated with IV cyclophosphamide. We retrospectively investigated 111 consecutive patients with progressive MS (21 PPMS and 90 SPMS) treated in an open label fashion with IV cyclophosphamide. We analysed clinical data (gender, age, duration of progression, primary versus secondary MS). The treatment response was assessed by EDSS change after 6 months and 1 year of treatment. The annual relapse average decreased from 1.92 before treatment to 0.39 during the treatment. Age and gender did not influence response to therapy. We did not find any difference of response between PPMS and SPMS. Duration of the progressive phase in SPMS was not a predictive factor of efficacy. A better response was noted in SPMS patients with surimposed relapses than in patients without relapses during the year before treatment (p<0.05). Furthermore, the better response in SPMS patients with relapses before treatment suggests that it is necessary to treat when MS is still in an inflammatory stage.

[Mitochondrial myopathy. Encephalopathy with lactic acidosis and cerebral infarction]. / Myopathie mitochondriale. Encéphalopathie avec acidose lactique et infarctus cérébraux.

A 21 year-old man presented with a history of sudden onset of aphasia and headache. CT showed a left parietal hypodensity and pallidal calcifications. The ECG showed a Wolff-Parkinson-White's syndrome. The patient then developed successively focal epileptic seizures, temper disorders, a cardiomyopathy, a pepper and salt retinopathy with hemeralopia, a left hemiplegia, deafness, and fever of unexplained origin. Left carotid angiography showed thin, irregular or occluded branches of the middle and anterior cerebral arteries. Blood muscle enzymes, lactate and pyruvate, were elevated with acidosis. Muscle biopsy revealed a mitochondrial myopathy and blood chemistry showed a severe deficiency of respiratory chain enzymes. Death occurred after 28 months. This case showed the diagnostic features of Melas, with some elements of the Kearns-Sayre syndrome. To our knowledge, this is the first case were serial angiographies allowed demonstration of arterial changes capable of explaining cerebral infarctions.

[Posttraumatic neurogenic hyponatremia with late onset]. / Hyponatrémie neurogène post-traumatique de révélation tardive.

Ten months following a severe head injury, a 26-year-old man developed a syndrome of inappropriate secretion of antidiuretic hormone (ADH) with a grand mal seizure occurring after an increased intake of non alcoholic beverages. The water loading test was negative but the sorbitol infusion test was positive. In the basal state, plasma concentration of ADH was inappropriate to plasma osmolality. ADH has also been measured during dynamic tests (infusions of sorbitol and of normal saline; complete and partial water restriction; propranolol and diphenylhydantoin treatments). In spite of the poor sensitivity of these measurements when ADH concentrations are low, our results indicate that the plasma osmolality threshold at which ADH secretion is inhibited was probably reset at a level lower than normal.

[Intraspinal hemangiopericytoma. 2 cases and review of the literature]. / Les hémangiopéricytomes intrarachidiens. Deux observations et revue de la littérature.

Two cases of intraspinal meningeal hemangiopericytomas are reported, one of which cervical and the other one dorsal with relapse. The anatomopathological features of the hemangiopericytomas are recorded and the nosological problems of their meningeal localizations are discussed. As in the case of intracranial meningeal hemangiopericytomas, the clinical, radiological and macroscopic features of intraspinal hemangiopericytomas--to the exception of a few particular cases--resemble those of other localizations of these tumours more than those of meningiomas, in the light of the review of twenty-eight cases to be found in the relevant literature. Treatment of such tumours hasn't as yet been well circumscribed. Surgical treatment may be facilitated by preoperative embolization. Radiotherapy must be associated to it, at least when removal is incomplete, because of frequent recurrence.

[Diagnostic and prognostic value of diaphragmatic electromyography and somatosensory evoked potentials in cervical spine and spinal cord injuries]. / Intérêt diagnostique et pronostique de l'électromyographie diaphragmatique et des potentiels evoqués somesthésiques dans les traumatismes vertébro-médullaires cervicaux.

SEP contribution to diagnosis is interesting but limited to hardly examined complete syndromes in an emergency care unit. The predictive value of SEP is high if electrophysiological data are correlated the 10th. day with the clinical status. A good prognostic value is shown when the clinical posterior column and pyramidal tract dysfunctions are equal in intensity and distribution, i.e. in complete syndromes or central spinal cord syndromes or Brown-Sequard's ones. However, not any correlation exists in cases of anterior spinal cord syndromes. Dg.EMG. is an easy, atraumatic useful tool for the clinician. It must be a systematic approach of the brain stem and cervical spinal cord phrenic centers vitality that may be involved by the trauma. When a respiratory deficiency occurs, it allows the diagnosis of a "peripheral" or "neurological" etiology. Its high prognostic value for m tor diaphragmatic function (increase or decrease) must be discussed before any therapeutic decision.

Rate of intravenous thrombolysis for acute ischaemic stroke in the North-of-France region and evolution over time.

The proportion of patients with ischaemic stroke treated by intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) is an indicator of quality of stroke care. The objective of the study is to evaluate the rate of i.v. thrombolysis in the North-of-France region and its evolution over time. We determined the proportion of inhabitants treated by i.v. rt-PA in 2009-2010 (period A; 8 stroke units, no telemedicine) and 2012 (period B; population campaigns, 12 stroke units with telemedicine in 5). We used hospital registries from the 12 stroke units, and population-based data were collected in a subpopulation of 226,827 inhabitants (5.6% of the whole population). 1,563 inhabitants received i.v. rt-PA for stroke (period A: 835 in 24 months; period B: 728 in 12 months). Hospital and population data were similar. Annual rates of thrombolysis increased from 103 per million inhabitants [95% confidence interval (CI) 85-125] to 181 (95% CI 157-209; relative increase 76%, 95% CI 67-83%). This rate increased in 12 districts (significantly in 6), but the increase was greater in districts where new stroke units, telemedicine, or both were implemented. In conclusion, although the proportion of patients treated was already high in period A, there was still place for improvement. Implementation of new stroke units, extension of the telemedicine network and new population campaigns are necessary to improve the rate of thrombolysis in several areas, to ensure an equal access to treatment over the whole territory. The next step is now to determine whether this high rate of i.v. rt-PA delivery at the population level translates into clinical results.

ANSO study: evaluation in an indoor environment of a mobile assistance robotic grasping arm.

OBJECTIVE: To evaluate the reliability and functional acceptability of the ''Synthetic Autonomous Majordomo'' (SAM) robotic aid system (a mobile Neobotix base equipped with a semi-automatic vision interface and a Manus robotic arm). MATERIALS AND METHODS: An open, multicentre, controlled study. We included 29 tetraplegic patients (23 patients with spinal cord injuries, 3 with locked-in syndrome and 4 with other disorders; mean SD age: 37.83 13.3) and 34 control participants (mean SD age: 32.44 11.2). The reliability of the user interface was evaluated in three multi-step scenarios: selection of the room in which the object to be retrieved was located (in the presence or absence of visual control by the user), selection of the object to be retrieved, the grasping of the object itself and the robot's return to the user with the object. A questionnaire was used to assess the robot's user acceptability. RESULTS: The SAM system was stable and reliable: both patients and control participants experienced few failures when completing the various stages of the scenarios. The graphic interface was effective for selecting and grasping the object ­ even in the absence of visual control. Users and carers were generally satisfied with SAM, although only a quarter of patients said that they would consider using the robot in their activities of daily living.

[Post-traumatic cerebral edema. Physiopathology and treatment]. / L'cedème cérébral post-traumatique. Physiopathologie et thérapeutique.

Severe head injury often produces complex intracranial displacements of the brain, resulting in widespread, often microscopic lesions. These are responsible for two types of edema: vasogenic edema, with outflow of molecules and fluid into the extracellular spaces by rupture of the blood-brain barrier and vasoplegia, and cytotoxic edema, with swelling of astrocytes due to membrane lesions. The connexions between these two types of edema are still obscure. Alterations in membrane phospholipids may impede function of Na-K pump enzymes, causing accumulation of water in the cell. Cerebral edema is responsible for intracranial hypertension and tentorial herniation, which in turn increase edema through venous compression, ischemia, and hypoxia. The least controversial anti-edema therapeutic measures include relative fluid and salt restriction, mannitol if called for, neuroplegia, in particular with diazepam and Gamma-OH, and assisted ventilation.