A. Benoilid

Reduction of the washout time between natalizumab and fingolimod

Drugs such as natalizumab (Tysabri) and fingolimod (Gilenya) are now available to treat multiple sclerosis (MS) and are usually proposed for patients with active MS. Several studies recently reported that the disease was frequently reactivated between 3 and 6 months after the withdrawal of Tysabri treatment.1–2 These results suggest the need for a therapeutic alternative that can be quickly introduced if Tysabri has to be withdrawn. However, there are also recommendations for a delay of 3 months between two immunosuppressive drugs. We extracted clinical data from the all patients in our region (Alsace, France) who had received at least one month of Gilenya treatment (n=164) between the 1 January 2012 and 1 January 2013. Some 59 patients in this cohort (36%) had switched from Tysabri to Gilenya, mainly due to positive JC virus serology (96.6%). All patients had stopped Tysabri at least 6 months before the time of data analysis, thus allowing us to evaluate the high-risk period (3–6 months) for MS reactivation. We then compared the subgroup of patients with and the subgroup of patients without relapses in terms of the mean delay between stopping Tysabri and starting Gilenya. We also compared the frequency of relapses in patients treated with Gilenya less than 3 months after stopping Tysabri and those treated 3 months or more after. The mean time on Gilenya treatment was 7 months (range: 1–12 months). All patients but three (94.9%) were treated with Gilenya for 6 months or more and were still receiving the treatment at the end of the study. Of the three patients who stopped Gilenya, one stopped because of disease reactivation (three relapses in 5 months) and two stopped because of side effects (gastro-intestinal symptoms) after 1 month. We did not find any differences between the two subgroups regarding age, sex ratio, Expanded Disability Status Scale (EDSS) score or disease duration. Eleven patients (18.6%) had at least one relapse. We observed eight patients (50%) with at least one relapse in the subgroup treated with Gilenya after a delay of 3 months or more (n=16) but only three patients (7%) in the group treated after a delay of less than 3 months (n=43) (p=0.02). The mean delay between the two drugs was 1.7 months (±0.55) for the whole cohort. However, in the subgroup without relapses the mean delay was 1.3 months (±0.32) versus 3.3 months (±1.1) in the group with relapses (p<0.05). Our results clearly argue in favour of an early switch between Tysabri and Gilenya instead of applying the classical washout period of 3 months or more. These results are in accordance with the recent studies showing frequent relapses in patients treated with Gilenya after a delay of 3 months or more.3–5 We recommend reducing as much as possible the delay between the withdrawal of natalizumab and the introduction of fingolimod, to reduce the likelihood of a reactivation of the disease during this high-risk period. One month could be a suitable delay, but this proposition will need to be confirmed in larger studies.

TDP43-Positive Intraneuronal Inclusions in a Patient with Motor Neuron Disease and Parkinson’s Disease

Background: The role of the 43-kDa transactivation-responsive DNA-binding protein (TDP43) in neurodegenerative diseases is not yet clearly established. Objective: To assess for the first time the presence of TDP43 in a patient with motor neuron disease (MND) and Parkinson’s disease (PD). Methods: A 78-year-old woman developed poorly dopa-responsive parkinsonism without cognitive alteration. Three years later, MND appeared and led to death in less than a year. Neuropathologic examination was performed. Results: We observed the presence of PD and MND lesions with TDP43-positive cytoplasmic inclusions in the spinal cord and bulbar nuclei but not in the dentate gyrus and neocortex. The MND was characterized by a severe degeneration of bulbar and cervical lower motor neurons. Numerous senile plaques and topographically limited neurofibrillary tangles were also observed. Conclusion: The mechanisms underlying the rare co-occurrence of PD and MND are still unclear. The assessment of an abnormal reactivity for TDP43 in our case might gain more insight into the pathophysiology of this association of two diseases. Further studies are needed to confirm these findings and to understand the role of TDP43 in neurodegenerative diseases.

Mitochondrial myopathy caused by arsenic trioxide therapy

Arsenic trioxide (ATO) has been successfully used as a treatment for acute promyelocytic leukemia (APL) for more than a decade. Here we report a patient with APL who developed a mitochondrial myopathy after treatment with ATO. Three months after ATO therapy withdrawal, the patient was unable to walk without assistance and skeletal muscle studies showed a myopathy with abundant cytoplasmic lipid droplets, decreased activities of the mitochondrial respiratory chain complexes, multiple mitochondrial DNA (mtDNA) deletions, and increased muscle arsenic content. Six months after ATO treatment was interrupted, the patient recovered normal strength, lipid droplets had decreased in size and number, respiratory chain complex activities were partially restored, but multiple mtDNA deletions and increased muscle arsenic content persisted. ATO therapy may provoke a delayed, severe, and partially reversible mitochondrial myopathy, and a long-term careful surveillance for muscle disease should be instituted when ATO is used in patients with APL.

Heroin inhalation-induced unilateral complete hippocampal stroke

A 33-year-old man presented to our clinic with amnesia 48 hours after his first heroin inhalation. Examination showed lateral tongue biting and anterograde amnesia demonstrated by impaired performance on verbal and visual Wechsler Memory Scale–Revised tests carried out 10 days after onset, suggesting hippocampal involvement. Magnetic resonance imaging (MRI) of the brain was performed 48 hours after heroin snorting and evoked cortical laminar necrosis (CLN) of the left hippocampus without vascular abnormality. This is the first description of complete hippocampal CLN as a complication subsequent to acute intranasal heroine abuse. While the pathogenic mechanism remains uncertain, our case provides a very specific MRI lesion pattern and highlights the risk of intranasal heroin uptake-induced neurological complication.

First Case of Human Cerebral Taenia martis Cysticercosis

ABSTRACT Taenia martis is a tapeworm affecting mustelids, with rodents serving as intermediate hosts. The larval stage (cysticercus) has been found before only rarely in humans or primates. We hereby describe a case of cerebral T. martis cysticercosis in a French immunocompetent patient, confirmed by DNA analyses of biopsy material.